@MedicalBooksStore 2012 Pelvic Pain

Human Anatomy and Physiology
PELVIC PAIN
CAUSES, SYMPTOMS
AND TREATMENTS
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Pain and its Origins, Diagnosis and

Treatments
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PELVIC PAIN
CAUSES, SYMPTOMS
AND TREATMENTS
MARY LOURDES LIMA DE SOUZA MONTENEGRO

EDITOR
Nova Biomedical Books

New York
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Library of Congress Cataloging-in-Publication Data

Pelvic pain : causes, symptoms, and treatments / editor, Mary Montenegro.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-62081-775-9 (eBook) 1. Pelvic pain. I. Montenegro, Mary.
[DNLM: 1. Pelvic Pain. 2. Chronic Disease--therapy. WP 155]
RG483.P44P44 2011
617.5'5--dc23
2011015625
Published by Nova Science Publishers, Inc. New York

Contents
Preface vii
Mary Lourdes Montenegro
Chapter I Pelvic Pain: Causes, Symptoms, and Treatments 1
Augusto Pereira-Sanchez, Tirso Perez-Medina,
Arantxa Martin Arias and David Abejon
Chapter II Local Use of Electrophonophoresis in the Treatment of Patients
with Immunologically Based Neuro-Vertebral Conflicts 45
Andrzej Dyszkiewicz
Chapter III Myofascial Pain Syndrome in the Pelvic Floor: Etiology,
Mechanisms, Symptoms, Diagnosis, and Treatment 77
F. Itza Santos, D. Zarza, L. Serra Llosa, F. Gmez Sancha,
J. Salinas, and E. Bautrant
Chapter IV Hormonal Modulation of Genitourinary Pain 109
Anna P. Malykhina and Gina M. Northington
Chapter V Pathophysiology of Endometriosis-Associated Pelvic Pain 131
Julia Arnold and Sylvia Mechsner
Chapter VI Chronic Non Bacterial Prostatitis/Chronic Pelvic Pain Syndrome 151
Ahmed S. El Hefnawy
Chapter VII Management of Pelvic Pain: What Is the Evidence? 173
Renato Seracchioli, Giulia Montanari, Elisa Geraci
and Stefania Alvisi
Chapter VIII Physical Therapy in Management of Women
with Chronic Pelvic Pain 187
Mary Lourdes Lima de Souza Montenegro
Chapter IX Pelvic Morphology: Its Role in the Differential Causes
of Pelvic Pain 199
Rajesh Rout and Colin Nnadi
vi Contents
Chapter X Skin Surface Electromyography in Chronic Prostatitis

Type III/Chronic Pelvic Pain Syndrome: A Fast and
Reliable Way for Diagnosis 211
Carlos Perez-Martinez and Beatriz Vargas-Diaz Irma
Index 221
Preface
Mary Lourdes Montenegro

Department of Gynecology and Obstetrics,
School of Medicine of Ribeirao Preto- University of So Paulo, Brazil
Chronic pelvic pain is defined as non-menstrual or noncyclic pelvic pain with duration of
at least 6 months, sufficiently intense to interfere with habitual activities requiring treatment.
Chronic pelvic pain was related for the first time in 1883 by Lawson Tait, a gynecologist that
observing women who stayed sitting at the piano a lot of time had symptoms similar to that
assigned nowadays to chronic pelvic pain, since then, the interest to study this disease comes
increasing. Despite of this, are great difficulties in establishing the primary cause of chronic
pelvic pain and consequently in proposing adequate treatment. This occurs mainly because
chronic pelvic pain involves a complex interaction between the gastrointestinal, urinary,
gynecologic, musculoskeletal, neurologic and endocrine systems. The estimated prevalence of
chronic pelvic pain is 3.8% among women aged 1573 years, ranging from 14% to 24%
between women in reproductive age. About 60% of these women never receive a specific
diagnosis and 20% never undergo any investigation to elucidate the cause of pain. In addition,
almost 40% of women who are seen at primary care units complain of pelvic pain, which
accounts for 4050% of gynecological laparoscopies, 10% of gynecological visits and
approximately 12% of hysterectomies. Additionally, chronic pelvic pain involves direct and
indirect costs exceeding 40 billion dollars a year only in United States. Despite of this, is still
little what is known about the physiopathology, prevalence, etiology and treatment of chronic
pelvic pain. Therefore this book comes to fill a space required within the scientific literature
describing and analyzing important concepts about chronic pelvic pain, and undoubtedly will
contribute to the spread of the known and the improvement of research about the disease.
In: Pelvic Pain: Causes, Symptoms and Treatments ISBN 978-1-61324-656-6
Editor: Mary Lourdes Montenegro 2012 Nova Science Publishers, Inc.
Chapter I
Pelvic Pain:
Causes, Symptoms, and Treatments
Augusto Pereira-Sanchez, Tirso Perez-Medina,

Arantxa Martin Arias and David Abejon
Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
Pain, is a common health problem that impacts in the quality of life of patient more than
other symptom. Chronic pain affect an important number of daily activities of patients such
work, sleep or sex life and cause a socio-economic problem of big magnitude.
People with chronic pain use a high number of health care resources such emergency,
diagnostics and outpatient services and generate a high cost of prescriptions for analgesia and
anti-inflammatory drugs. The 25% of people with chronic pain lose their jobs, decrease their
work opportunities and is the second reason for claiming incapacity benefits1.
Between 2007-2008 the National Center for Health Statistics in United States estimated a
7,0 million emergency visits, in which abdominal pain were the primary reason for the visit.
Approximately 15% (nearly 1 million each year) were identified as acute pelvic pain (APP).
The prevalence of chronic pelvic pain (CPP) in women are over 25%, the estimated direct
medical costs of CPP are $881.5 million per year, but globally direct and indirect costs of
these disease approach to $3 billion per year2.
These epidemiological data and the economic impact could be significantly higher, if we
adopt the current definition of pain by the International Association for the Study of Pain
(IASP): Pain is an unpleasant sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage.
2 Augusto Pereira-Sanchez, Tirso Perez-Medina, Arantxa Martin Arias et al.
Pain in gynecological disease can be classified from different points of view, depending
on anatomical location, cause, duration, severity and characteristics. The current knowledge
of the pathophysiology of pain, classified the pain, avoiding the psychogenic pain as:
Neuropathic pain results from injury of peripheral or central nervous system.

Nociceptive pain arises from the somatic or visceral nociceptive stimulation.
Neuropathic pain is caused by inappropriate behavior of the nervous system due to
damage, disease or trauma. The characteristics of pain are:
Sharp, intense, shocking or penetrating pain.

Confined to a small area.
Persistent and does not respond well to conventional therapies.
Nociceptive pain is caused by stimulation of nociceptive receptors. The characteristics of

pain are:
Muted or intense pain.

Control the pain when we remove the cause.
Acute or chronic.
I. Neuropathic Pain in Gynecology

Neuropathic pain is caused by damage at the lumbar or sacral plexus in the peripheral
nervous system (PNS) and it is cause of perineal pain.
Peripheral Nervous System (PNS) [3]
a) Perineal Sensitivity at Lumbar Plexus
Table 1. Lumbar nerves and innervations area
Nerve Sensitivity
T12-L1: iliohypogastric: genital branch Suprapubic region extending to genitals
L1: ilioinguinal: genital branch. Pubic mound, pubis and labia majora
L1-L2: Genitofemoral: genital branch Pubis, labia majora and round ligament of
uterus
L2-L3: Lateral femoral cutaneous Lateral thigh to the knee
L2-L4: Obturator Inner thigh and knee.
Pelvic Pain: Causes, Symptoms and Treatments 3
b) Perineal Sensitivity at Sacral Plexus
Table 2. Sacral nerves and innervations area
Nerve Sensitivity
S1-S3: Posterior femoral cutaneous: Perineal Skin on gluteus, adjacent perineum and labia
branch majora
S2-S3: Sacral S2 and S3: cutaneous perforant Skin on gluteus and adjacent perineum.
branch
S2-S4: Pudendal: 3 branches
Dorsal nerve of clitoris Skin and vulvar mucosa reaching the
Clitoris branch inguinal canal.
Pubic branch
Perineal Skin side of the perineum, labia majora and
Superficial perineal branch minora, lower third of the vagina and urethra.
Deep perineal or muscle urethral branch. Levator ani, superficial and deep transverse
perineal, bulbocavernous, ischiocavernosus and
coccygeal muscles. Urethral mucosa.
Inferior anal Anal canal and caudal part of rectum,
fourchette and perianal skin, dorsal cutaneous
perineal terminations
S4-S5: Anococcygeus Skin on coccyx
Lumbar Neuralgia [4, 5]
In the lumbar plexus we identified three lumbar nerves with common characteristics: the
iliohypogastric (T12-L1), ilioinguinal (L1) and genitofemoral (L1-L2) nerves with the same
PNS plexus origin, all of them cross the inguinal canal and have a genital branch that gives
sensitivity to the female external genitalia.
We identified other lumbar nerve that can be damaged in gynaecologic surgery: the
lateral femoral cutaneous nerve (L2-L3).
Causes of Neuropathy in the Lumbar Region

a) Direct trauma to nerve: Pfannenstiel incision extended beyond the lateral border of
the lower rectus abdominis muscle with a:
Direct surgical trauma.

Inclusion of the nerve by suture or fascia repair procedure.
Entrapment by scar tissue or neuroma after surgery.
b) Nerve ischemia: interruption of blood flow supply at intrapelvic vascular surgery,

aorta or renal transplantation.
c) Direct or indirect compression of the nerve by hematomas, valves or retractors.
A. Iliohypogastric Neuralgia [6]

Iliohypogastric nerve penetrates in transverse abdominal muscle near the iliac crest,
standing between it and the internal oblique muscle, crosses and reaches the skin through an
opening of 2-3 cm in the fascia of external oblique muscle above the superficial inguinal ring.
Causes
Inguinal herniorrhaphy and appendectomy.

Hysterectomy.
Caesarea.
Trauma or sports injuries tears of the lower abdominal muscles.
Pregnancy and abdominal expansion in the 3rd quarter.
Location: lower abdominal incisions (Pfannenstiel)

Clinical and physical examination
Burning sensation or pain in the inguinal surgical incision or suprapubic area, may
radiate to the external genitalia.
Hyperesthesia or hypoesthesia in the course of the Iliohypogastric nerve.
Symptoms are similar to trochanteric bursitis, but are refractory to the conventional
treatment.
Tactile surface exploration
Q-tip test in groin, suprapubic and hips. The loss of sensation is usually minimal and
not problematic.
Deep exploration
Positive Tinel's sign: pain is presents when compression the scarring area or the
entrapment location.
Lower abdominal skin reflexes
The friction on the skin in the abdomen, from the edge to the midline, causing
seizure of the skin, abdominal muscle contraction with displacement of the umbilicus
and the Linea Alba (white line thats connects xiphoid with pubic symphysis and
crest) to the side of the stimulation.
B. Ilioinguinal Neuralgia [6]

Ilioinguinal nerve emerges from the lateral border of psoas muscle; it traverses the
anterior abdominal wall to the iliac crest just inferior to the hypogastric nerve.
Causes
Inguinal hernia repair or appendectomy.

Pelvic surgery, TVT, TOT.
Hysterectomy, radical hysterectomy and lymphadenectomy.
Caesarea.
Trauma or sports injury.
Spontaneous (rare).
Location: Compression of ilioinguinal nerve as it passes through transversus abdominis

muscle at the level of the anterior superior iliac spine.
Paresthesias, pain, burning sensation and numbness in the lower abdomen. The pain
irradiation is to the external genitalia, sometimes at the upper-inner thigh and never
below the knee.
The weakness of the abdominal wall muscles, creates a bulge in the front of the
abdomen (differential diagnosis with inguinal hernia).
Examine the oblique muscles of the abdomen with the trunk rotated: Pain was
aggravated by the extension of the hip or lumbar spine.
The patient with the ilioinguinal nerve affected, has a bent forward position as the
novice skier.
Q-tip test in the hips and groin area: discover a sensory deficit in the inner thigh or
labia.
Deep exploration
Positive Tinel sign on ilioinguinal nerve at the point at which crosses the transverse
abdominal muscle.
Pain may also be reproduced with a medial palpation of anterosuperior iliac spine.
Lower abdominal skin reflexes (see above)
C. Genitofemoral Neuralgia [6,7]

Genitofemoral nerve pierces the anterior surface of the psoas major muscle at the level of
L3-L4 and descends on the fascial surface of psoas major muscle past the ureter. The genital
branch continues along the psoas major to the deep inguinal ring and enters the inguinal
canal. In females, it travels with the round ligament of the uterus and provides cutaneous
sensation to the labia majora and adjacent thigh.
Causes
Inguinal hernia repair or appendectomy.

Hysterectomy, radical hysterectomy.
Caesarea.
Intrapelvic trauma or retroperitoneal hematoma.
Location: The entrapment of genitofemoral nerve can lead at any point in its course.
Pain and paresthesia in the region in the distribution of genitofemoral nerve: groin,
labia and medial thigh.
There hypoesthesia on the anterior thigh, below the inguinal ligament (differential
diagnosis with iliohypogastric or ilioinguinal nerves).
The pain may worsen with internal or external rotation of the hip, long walks,
stooping, climbing stairs, and hyperextension of the hip. It may be ameliorated by
recumbency and flexion of the thigh. On rare occasion it can be responsible for
chronic low lateral pelvic pain.
Positive Q-tip test with the application of light.
Deep exploration
Positive Tinel's sign with nerve compression, the pain is present in the groin area.
Geigel reflex (cremasteric reflex in male) (L1-L2)
Friction inner thigh and contraction of the external oblique muscle.
D. Lateral Femoral Cutaneous Neuralgia or Meralgia Paraesthetica [6]
Lateral femoral cutaneous nerve, has its origin directly from the lumbar plexus. It travels
lateral to femoral nerve underneath the inguinal ligament to innervate the skin of the lateral
thigh.
Cause: The nerve can be injured by:
Trauma or penetrating wounds of the thigh.

Inguinal hernia
Urological surgery
Hysterectomy. Radical hysterectomy
Other factors: Pregnancy, obesity, diabetes mellitus.
Location: Lateral femoral cutaneous nerve entrapments when it crosses the "inguinal
ligament" at its origin from the anterior iliac spine.
Clinic and physical exploration
Numbness, paresthesias or pain in the upper outer thigh. Exceptionally, there may be
bilateral.
Symptoms may worse if patient is standing or walking for long periods, sometimes in
obese patients, the sitting position can increase the pain.
Tactile surface exploration: not supported some clothes and a belt
Q-tip test: hyperesthesia or dysesthesia in the corresponding area, sometimes find an

anesthesia areas.
Varying degrees of disturbance in the sensibility of the outer side of the thigh,
especially with temperature.
Deep exploration
Pain with palpation in the inguinal ligament, medial to the anterior superior iliac
spine.
Reverse Lasgue sign: The pain is better when the hip is flexed and it is worse on
hyperextension of the leg.
Reflexes: Lateral femoral cutaneous nerve is exclusively sensitive. There is no motor

impairment, or alteration of tendon reflexes.
Differential diagnosis of cutaneous nerves

Major diagnostic criteria:
History of a surgical procedure in the lower abdomen.

A defined area of hypoesthesia or hyperesthesia in the region of nerve.
The infiltration of local anesthetic into the affected area, should provide symptomatic
relief.
In patients with persistent pain and paresthesia in the inguinal region
1. Ilioinguinal nerve block: assessing symptom relief

2. L1-L2 paravertebral block: to assess symptom relief.
3. Take a decision on surgical decompression of ilioinguinal or genitofemoral nerve.
E. Obturator Neuralgia [8]
Obturator nerve also emerges from lumbar plexus, descending more medially than the
femoral nerve, exiting the pelvis through the obturator foramen where it innervates the thigh
adductors and a small cutaneous area in the medial thigh.
Cause: Obturator nerve may be compressed into the obturator foramen by:
TVT, TOT
Radical hysterectomy
Bilateral tubes ligation
Obturator hernia
Inguinal hernia
Fractured pelvis
Neoplasia
Inflammatory process of the hip.
Pain in the medial thigh with radiation behind the knee and into the hip is most
common, the pain may be dull, sharp, shooting, or burning and increased with
exercise, prolonged standing, and prolonged sitting.
Howship-Romberg phenomenon: it is a pathognomic sign, the pain inside of the knee
joint.
Paresthesias in the innervate skin area.
Limited upright posture
Loss of sensation in the mid inner thigh.

The adductor motor weakness may be present andis cause of walk with an
abnormally abducted hip.
Deep exploration
Vaginal or rectal palpation of the obturator canal duplicate the patients symptoms.
Crossing the legs while sitting may exacerbate the pain
Loss of thigh adduction and circumduction of the leg (predominance of the
abductors)
Loss of strength of internal and external rotation
Adductor reflex (L2-L4), with gaping legs striking the medial condyle of the femur
causing a reflex contraction of the adductor muscles.
Sacral Neuralgia
In the sacral plexus, we identify three sacral nerves: the pudendal nerve (S2-S4) has three
terminal branches: inferior rectal nerve, perineal nerve and dorsal nerve of the clitoris that
gives a extensive genital sensitivity in the pelvic-perineum area such anal canal, caudal or
lower part of the vagina, urethra and rectum, clitoris, pubis or vulva and pelvic floor muscles.
Also, perineal branch of posterior femoral cutaneous nerve (S1-S3) and cutaneous
perforating branch of sacral nerve (S2-S3), both of them give sensitivity to the gluteus skin,
perineum and adjacent labia major.
Posterior Femoral Cutaneous Neuralgia
The posterior femoral cutaneous nerve is a sacral nerve, exiting the pelvis through the
greater sciatic foramen below the piriformis muscle. The perineal branches are distributed to
the skin at the upper and medial side of the thigh.
Pain and loss sensory in the postero lateral side of thigh (not below the knee). Skin
irradiation to buttocks, perineum, labia majora or adjacent
In general, hyperesthesia or dysesthesia in the area concerned, and sometimes areas
of anesthesia.
Q-tip test: a disorder of sensation in all its forms in the posterior and lateral thigh.
Deep exploration
Tinel's sign positive when palpation of the posterolateral thigh.
Reflexes: The posterior femoral cutaneous nerve is a sensitive nerve. No motor or deep
tendon reflexes are present.
Pudendal Neuralgia
Anatomy of pudendal nerve
A. First segment, from its origin in the sacral spinal segments S2, S3 and S4 to the
presacral region.
B. Second segment (Infrapiriforme canal). Enters the gluteal region under the piriformis
muscle and crosses the sacrospinous ligament and contact sacrotuberous ligament.
C. Third segment (Alcock's canal). Moves under the levator ani muscle, along the ischial
tuberosity, in a sheath of muscle fascia that forms the internal stop channel Alcock.
The presence of neuropathic signs and symptoms in segments or branches of the
pudendal nerve identifiy the damaged nerve pathway, all these manifestation are called:
perineodynia, urethrodynia, vestibulodynia or vulvodynia.
B.1. Vulvodynia [9,10]

The International Society for the Study of Vulvovaginal Disease (ISSVD) defines
vulvodynia as vulvar discomfort, most often described as burning pain, occurring in the
absence of relevant visible findings or a specific, clinically identifiable, neurological

disorder
This chronic vulvar discomfort within the female genitalia for more than 3 months
without other dermatological lesions or gynecological causes, is known as vulvodynia. In
addition to burning, sensations often are described symptoms as irritation, stinging, rawness,
aching, stretching, throbbing, sharp, knife-like pain and an important consideration are that
other diseases (infections, allergic dermatitis or vulvar dermatoses, atrophy due to estrogen
deficiency) that can cause chronic vulvar pain may coexist with vulvodynia.
Causes: The United States Conference on Vulvodynia of the National Institutes of Health
in April 2003, correlated the origin of pain in the pudendal nerve, levator ani or pelvic pain
with:
Awareness and communication between nerves cross.

Alterations and amplification of sensation.
Gene expression for susceptibility to pain.
Referred visceral pain.
Myofascial pain syndrome in women with painful points.
The association and the overlapping of symptoms between vulvodynia provoked and
interstitial cystitis:
Possible common origin of both diseases.

Vestibule and bladder are innervated by unmyelinated C nociceptive fibers.
Classification of vulvar pain by (ISSVD) [11]: Since October 2003, the ISSVD
classified the vulvodynia in two major categories basis on the site of pain, whether it is
localized or generalized; and if the pain is provoked, unprovoked, or mixed:
1.- Vulvar pain related to a specific disorder:
Infection: candidiasis, trichomoniasis, herpes simplex virus
Inflammatory: lichen simplex chronicus, lichen sclerosus, lichen planus, atrophic
vaginitis, immunobullous disorder
Neoplasm: Paget's disease, squamous cell carcinoma
Neurological: herpetic neuralgia.
2.- Vulvar pain related to a nerve compression: refers to several types of vulvar
discomfort occurring in the absence of relevant visible infectious, inflammatory, or neoplastic
findings and in the absence of a specific clinically identifiable disorder of any kind (ie,
idiopathic). The most common presentations are: Vulvodynia, or hemivulvodynia,
vestibulodynia and clitoridynia
Generalized or located.
Provoked, unprovoked or mixed.
Sexual, non sexual or both.
The pain related to nerve damage, included:
a) Dysesthetic vulvodynia, also called generalized vulvodynia or generalized vulvar

dysesthesia or unprovoked vulvodynia.
b) Vulvar vestibulitis syndrome (VVS), also called vulvar vestibulitis or localized
vulvar dysesthesia or provoked vestibulodynia.
1. Dysesthetic vulvodynia [12,13]:
A generalized vulvodynia, usually is defined as vulvar burning that has no obvious cause and
is not limited to the vestibule.
Symptoms location: Hymen, introitus, small or minor vestibular glands, Batholin's

glands, paraurethral glands (Skene's glands), vestibule, labia minora and majora. Some
patients also refer pain in the clitoris, perineum, pubis, anus, groin, and the inner thighs.
Burning, stinging, rough or dull pain at rest. The pain is chronic, continuous and not
provoked by any cause. Sitting or walking can cause pain.
No pain in response to touch or pressure on the vulva. Symptoms do not necessarily
occur during sexual intercourse or bicycle riding, but may increase the discomfort.
They may also have varying degrees of localized vulvar erythema.
2. Vulvar Vestibulitis Syndrome (VVS) [14,15,16]
A localized inflammation of the vestibule, often begins suddenly, following an infection or

trauma.
Burning is located in the vestibule and is caused by pressure or friction. In addition

VVS symptoms include an extremely tender, dry, or raw vestibule, stinging or
irritation of the vestibule, a sensation of tight skin in the vestibule, redness of the
vestibule, pain that is so severe as to preclude intercourse
The majority of women with VVS only have symptoms during or after the vestibule
is touched, sexual intercourse or tampon insertion and are present in the
gynecological examination, with prolonged sitting activities such bicycle or
horseback riding and jogging or wearing tight pants.
Urinary symptoms as urgency, urinary frequency, nocturia and pain relief with
micturition are common, but there is not symptoms for diagnostic criteria.
Friedrich criteria [17]
Intense pain with vestibular palpation or vaginal penetration.

Increased sensitivity to pressure, located at vestibule.

Physical findings limited only to varying degrees of vulvar erythema.
Location of pain areas applying a cotton swab in the vestibule at 2, 4, 6, 8 and 10

hourly and classified as mild, moderate and severe
Mild pain when applying pressure in hymenal caruncles, maximum in hymenal
remnants and near Bartholin glands.
Prior vulvodynia diagnoses, it is necessary to exclude other vulvar and vaginal
diseases cause of pain and evaluate the integrity of the vulva skin, the vaginal
mucous, with normal vaginal smears and without infection or skin diseases.
B.2. Pudendal Nerve Entrapment Syndrome (Pnes)
The PNES was communicated by Amarenco [18] in 1987 and described by Shafik [19]
et al. in 1991. The pudendal nerve compression in the Alcock's canal and/or in the "clamp"
between the sacro-spinal and the sacro-tuberous ligaments can induce pudendal neuropathy.
Causes:
Bicycle (the most classical one)

Trauma on the coccyx
Constipation with dyschesia (induces perineal descent)
Delivery
Pelvic trauma
Traction on the pelvis during orthopedic surgery
Sacro-spinal fixation
Classification: according with the entrapment location and to evaluated the surgical
access [20]:
Type I: at the exit of the greater sciatic notch in concert with piriformis muscle
spasm.
Type II: at the level of the ischial spine, sacrotuberous ligament, and lesser sciatic
notch entrance.
Type III: in association with obturator internus muscle spasm at the entrance of the
Alcock canal.
Type IV: distal entrapment of terminal branches.
Clinic and physical exploration: The diagnosis of PENS is essentially clinical. There
are no specific clinical signs or complementary test of this disease, but three clinical signs
suggest the diagnosis: the asymmetry of sensibility, positive "skin rolling test" and pain at the
level of the pudendal nerve. Perineal descent more than 2 cm increases the risk. However, a
combination of criteria can be suggestive of the diagnosis.
Nantes diagnostic criteria (2006) [21]

1. Essential criteria
Pain in the territory of the pudendal nerve: from the anus to the penis or clitoris -
Pain is predominantly experienced while sitting
The pain does not wake the patient at night
Pain with no objective sensory impairment
Pain relieved by diagnostic pudendal nerve block
2. Complementary diagnostic criteria
Burning, shooting, stabbing pain, numbness

Allodynia or hyperpathia
Rectal or vaginal foreign body sensation (sympathalgia)
Worsening of pain during the day
Predominantly unilateral pain
Pain triggered by defecation
Presence of exquisite tenderness on palpation of the ischial spine
Clinical neurophysiology findings in menor nulliparous women
3. Exclusion criteria
Exclusively coccygeal, gluteal, pubic or hypogastric pain

Pruritus
Exclusively paroxysmal pain
Imaging abnormalities able to account for the pain
4. Associated signs not excluding the diagnosis
Buttock pain on sitting

Referred sciatic pain
Pain referred to the medial aspect of the thigh
Suprapubic pain
Urinary frequency and/or pain on a full bladder
Pain occurring after ejaculation
Dyspareunia and/or pain after sexual intercourse
Erectile dysfunction
Normal clinical neurophysiology
Pelvic and Perineal Neurological Examination
A. General management of patients with vulvar pain
Medical history inquires about symptoms, mental status, sexual activity, diet,
feminine hygiene, and medications.
Pelvic examination: Vulva and vaginal exploration searching redness, erosion,
crusting sores, dryness, hypopigmentation and pallor.
Neurologic examination looking for neuropathic signs such allodynia and
asymmetric feelings using a swab test palpation (Q tip) to identify the location and
severity of pain or warm test detection (threshold).
Cultures of mycoses (Candida) and bacteria (Streptococcus Agalactiae). Microscopic
evaluation of vulva or vaginal secretions to detect possible mycoses infection,
vaginal ph and increases the number of polymorphonuclear leukocytes.
Use a magnifying lens or vulvoscopy to identify abnormalities and study the
inflamed areas.
Cutaneous specific biopsy in the suspicious areas.
B. Signs of neuropathic pain: The identification at the anamnesis of one or more of the
following signs in the pelvic or perineal area, should make us think of peripheral neuropathic
disease:
1. Allodynia: pain stimulus that produces pain. Pressure eg cotton.

2. Formication: sensation of insects crawling on skin (ants)
3. Paresthesia: abnormal sensation of burning, tingling, numbness or foreign body.
4. Skin changes: the sign of involvement of autonomic fibers can observe changes in
the skin of the buttocks: "marble" or "orange peel"
5. Inflammation, caused by excessive nerve stimulation.
6. Hyperalgesia: increased response to painful stimuli.
7. Hypoalgesia, decreased response to painful stimuli.
8. Dysesthesia, sensation produced by stimulation improper.
9. Metestesia: prolonged response to stimuli.
C. Exploration of neuropathic pain [22,23,24]
a) Direct examination: is made through the palpation of superficial nerves

b) Indirect examination: the exploration of nerve function:
Sensitivity aware
Status of muscles innervated by the nerve: contraction tone.
Securing the driving reflexes
Innervated organ secretions
c) Electrical exploration: the study allows:
Evaluated the nerve function through the electrical response.

Produce a nerve excitation to obtain a sensitive, sensory, motor or secretory
response.
D. Exploration of the motor function: The reflex is the motor response cause after a
stimuli. The reflex provides information on the integrity of the nervous system. We classified
the reflexes as:
1. Normal: are simple segmental reflexes, are present in healthy individuals and may
include:
Deep reflex.
Superficial reflex.
2. Pathological: are caused by a pathological stimuli or superficial muscle strain but

differ in that they can not be induced in normal subjects and are more complex than the
simple segmental reflex.
Exploration of perineal reflexes (S2-S4)
Clitoris reflex.
Bulbocavernosus reflex.
Perineal reflex.
The tactile stimulation with a cotton swab to the clitoris, perineal or bulbocavernosus
muscle cause an involuntary contraction of the anal sphincter
F. Exploration of the sensory function: The human being connected with the external
environment through the senses. The feelings that we can perceive are called:
Sensory sensations: sight, smell, hearing and taste

Sensitive feelings, would somatoesthetic sensitivity.
a) Superficial or exteroceptive sensors: The receptors located on the surface, provide

information about changes in the environment, skin sensitivity to grasp:
The light touch

Pressure
Temperature
Superficial pain
Examination: Using a piece of cotton, a brush or fingertips.

You will be playing on, different parts of the skin and the mucous membranes.
Avoid putting pressure on the excited points
The excitement should be a simple contact.
Exploration of superficial perineal sensitivity (S2-S4): The cotton swab test or Q-tip
test consists of using a cotton swab or Q-tip to palpate multiple vulvar and vestibular sites at
S2-S4 areas with the Cotton swab and blunt part searching differences of sensitivity to
identify the injured nerve.
b) Deep or proprioceptive sensors: The receptors are located at the innermost. Reports on
body movements and position in space, ie sensitivity from the bones, muscles and joints are
of various types and capture:
Deeper pain
Pressure
Proprioception. Sense of joint position and muscle
Exploration of deep perineal sensitivity: The exploration is to compress the muscle

mass or tendons accessible pinch:
Usually a moderate compression of the muscles and tendons is painless.

In certain pathological conditions the muscles are sensitive to the slightest pressure
(polyneuropathy, myositis, etc.).
There are other diseases where the strongest compression is painless (tabes).
a) Rolling test: The displacement of the skin and subcutaneous tissue on the route of the
nerve branches explored cause the painful syndrome.
b) Tinel sign25: The compression of the nerve trunk in the affected area, cause distal
radiation of pain.
c) Valleix phenomenon: The compression of the pudendal nerve reproduces the
proximal and distal radiation of pain. The nerve compression should be performed in
sciatic spine or Alcock's canal
G. Sensitivity of the organs or interoceptive sensors: The receptors are called

interceptors report visceral activity and capture the pain with compression.
Table 3. Corresponding visceral sensory nerve convergence-projection fields6
Somatic nerve Dermatome Viscera field

Iliohypogastric T12-L1 Ovary, distal fallopian tubes
Ilioinguinal L1 Proximal tube, uterine fundus
Genitofemoral L1-L2 Proximal tube, uterine fundus
Lateral femoral cutaneous L2-L3 Fundus, lower uterine segment
Pudendal S2-S4 Fundus, lower uterine segment, cervix, bladder
distal, ureter, upper vagina, rectum
II. Nociceptive Pain in Gynecology

Nociceptive pain is caused by stimulation of an intact nervous system and it is the origin
of pelvic pain.
Autonomic Nervous System (ANS)
a) Infradiaphragmatic plexus
Table 4. Visceral sensory innervations of the abdominal and pelvic organs
Primiary plexus Secondary plexus Tertiary plexus Sensitivity

Thoracic aortic Celiac plexus or Celiac plexus Hepatic plexus, Pancreatic Liver, Pancreas, Speen
plexus solor plexus. plexus, Splenic plexus
Superior Gastic plexus Small intestine, Ascenting,
mesenteric plexus part transverse colon
Part of pancreas
Aorticorenal plexusAbdominal aortic plexus. Kidney Adrenal gland
Lumbar or Presacral nerves Inferior Renal plexus. Suprarenal Left colon Sigma, Rectum
lumbo aortic or interiliac mesentreric plexus plexus, Ovarian/Spernatic Adnexa
plexus plexus plexus
Hypogastic or Superior Superior hemorrhoidal Anal Canal
pelvic plexus hypogastric plexus plexus
Sacral Inferior Vesical plexus, middle Bladder, Rectum,
plexus hypogastric rectal plexus, Genitals organs
plexus Uterovaginal plexus
b) Pelvic autonomic plexus
Table 5. Visceral sensory innervations of the genital tract
Plexus Origin Branch Sensitivity Plexus

Inferior Sympathetic NS Vesical plexus T10-L1: Hypogastric Bladder and urethra
hypogastric or nerve Pubis, labia majora.
pelvic plexus Uterine cervix, vagina
Middle rectum plexus Middel rectum
Uterovaginal plexus Pubis, labia majora
(Frankenhuser) Vagina, vestibule
Clitoris, Uterus.
Ovarian plexus Sympathetic NS T10-T12: Ovarian Tubes and ovary
nerve Broad ligament
Uterine fundus
Pelvic nerve Parasympathetic S2-S4: Erector or Bladder, rectum,
NS pelvic nerve descending colon, urinary
genital tract and uterine
cervix
Superior Parasympathetic L4: Sacral concavity Broad ligament
Internal iliac NS
Sacral plexus 30% ANS Pudendal plexus S2-S4: Pudendal Perianal skin, vulva,
nerve perineum, lower third of
vagina, urethra, clitoris
and vestibule
Basis on the difference in the pattern of innervations, nociceptive pain can be

classified as:
A. Pelvic Somatic Pain
The somatic nervous system (SNS) includes all structures of the central and peripheral
nervous system (CNS and PNS). SNS is responsible of conducting afferent sensitive and
motor information from the pelvic musculoskeletal system.
Persistent bad positions or muscle imbalances can change the mechanics of the pelvis
joint and cause pelvic pain. In the musculoskeletal factor are involved the sacroiliac, pubic
symphysis and sacrococcygea joints.
The muscular layer of the pelvic floor includes three important muscles: levator ani,
piriformis and obturator internus. In this part of the chapter will be described the myofascial
pelvic pain syndrome in women (MPPS), the exploration, sign and symptoms, pharmacologic
treatment and physical therapy.
Myofascial Pain Syndrome of the Pelvic Wall Muscles
Causes: inflammation, acute or repeated trauma, exposure to cold and other stressors can
trigger muscle pathogenic mechanisms, which give rise to the fascia, muscle and sometimes
containing other flexible and elastic tissues neighbors lose their elasticity
This fascia and muscle shortening and pain, resulting in a zone, a taut band within which
houses a hyperirritable point, the so-called "trigger points".
a) Levator ani myofascial syndrome [26]

Caused by spasm of the levator ani muscle.
Clinic: Chronic pain in the upper rectum, weight or burning sensation, aggravated by
defecation or by pressure applied to the levator ani muscle.
Diagnostic criteria
Recurrent rectal chronic pain

Episodes of 20 minutes or longer
Exclusion of other causes of rectal pain as inflammatory bowel disease, ischemia,
abscess, fissure, hemorrhoids or rectal ulcer.
For at least 12 weeks (not consecutive) in the last 12 months.
b) Obturator myofascial syndrome [27]: Caused by spasm or injury of obturator

muscle, similar symptoms are present as related before for obturator neuralgia.
d) Piriformismyofascialsyndrome[28,29,30]:Caused by spasm of pirifomis

muscle. The sciatic nerve can go through the pirifomis muscle as normal
anatomic variant. In piriformis myofascial syndrome are present sciatica
symptoms, pain may be radiate from gluteal region to backside of the knee.
The pirifomis muscle is an external rotator of the leg. The rotation of the leg
resistance exercise reproduces the pain.
The major findings include

Buttock tenderness extending from the sacrum to the greater trochanter and
piriformis tenderness on rectal or pelvic examination.
Symptoms are aggravated by prolonged hip flexion, adduction, and internal rotation,
in the absence of low back or hip findings.
Minor findings may include
Leg length discrepancy.

Weak hip abductors.
Pain on resisted hip abduction in the sitting position.
Myofascial involvement of related muscles and lumbar facet syndromes may occur
concurrently.
B. Pelvic Visceral Pain [31,32,33,34]
The pelvic pain in genital organs is conducting by autonomic nervous system (ANS). The
severity of pelvic pain depends on the number of nerve fibers and sensitive receptors located
in the pelvic organs.
Structures with a low rate of sensitive receptors or innervations are: visceral serous or
endometrium.
Structures with a high rate of sensitive receptors are: the hollow pelvic viscera as uterus
or fallopian tubes, the capsule of solid organ as ovary and parietal serous.
Visceral pain comes from three different ways: the mechanical, inflammatory and
ischemic. Mostly pathologies which cause pelvic pain combine several of these mechanisms,
although one of them predominates.
1. Mechanics: the distension or contraction of the muscular layers of the uterus or tubes,
can cause pelvic pain. Secondarily to the uterine contraction, the blood flow may decrease in
the organ and increase the pain.
The distension of the capsule at the ovary, is other important mechanism to produce a
gradual pelvic pain.
These are the main gynecologic diseases that are responsible of pelvic organ distension:
Ectopic pregnancy.
Hydrosalpinx or sactosalpinx.
Incomplete abortion.
Complicated uterine fibroid: degeneration.
Adenomyosis.
Endometrial polyps.
Uterine malformation.
Asherman syndrome.
Imperforate hymen.
Transverse vaginal septum.
Cervical stenosis.
Rupture follicular or corpus luteum.
Ovary Cyst: Torsion, hemorrhagic or rupture of an ovarian cyst.
Ovarian hyperstimulation syndrome.
2. Inflammatory: The release of biochemical mediators involved in the inflammatory or

infection response, are powerful pain stimulators. The rupture of ovarian cyst, the bleeding
and spillage of its content into the intraperitoneal cavity may cause a chemical peritonitis. The
deeply infiltrating disease as endometriosis or cancer may be in relation with nerves
compression or infiltration in the subperitoneal pelvic space by the implants.
These are the main gynecologic diseases involved in the pelvic inflammatory process:
Pelvic inflammatory disease (PID, presented as pyosalpinx or fallopian tube abscess)

Pelvic neoplasia.
Endometriosis.
Endometritis.
Salpingitis.
Intraperitoneal adhesions.
Retrograde or ovulation bleeding (Mittellschmerz).
3. Ischemic: The interruption of blood supply to the pelvic organ may cause embolism
and primary or secondary thrombosis in the twisted vascular pedicle. The concentration of
tissue metabolites release in the ischemic process may cause irritation and is the origin of
pelvic pain.
These are the ethiopathogenic mechanism of pain in:
Adnexal torsion (ovary, paraovary and/or tubes).

Ovarian vein trombosis
Torsion of a submucosal or subserous pedunculated uterine fibroid.
1. Mechanical
a) Ectopic pregnancy [35,36,37,38,39]
The pregnancy occurs out of its usual location, the uterus. It affects 1/1000 pregnancies
and the most common location is the tube (96-99%). It can appear in the ovary, cervix, and
abdominal cavity, but these locations are much less usual. Among tubal pregnancies, the most
usual are the ampullaries (68%). Ampullary portion of the tube is wider by allowing
distension, which keep the patient as asymptomatic. In these cases break is usually older. On
the contrary, isthmic location pregnancies (8-25%) use to have early symptoms due to the
large musculature that has the tube in this segment. In these cases the strain is smaller and
more symptomatic, and rupture occurs much earlier. Rupture occurs early as well in cases of
interstitial pregnancies, becoming more complicated due to being more vascularised. The
pregnancies located in the flag often asymptomatic, until tubal abortion occurs. In these cases
the tube has not distension, but pregnancy may develop until the vasculature is not sufficient
to produce gestational sac development. Then tubal abortion occurs whose symptoms are
caused by peritoneal irritation.
Clinical manifestations of ectopic pregnancy are abdominal pain and vaginal

hemorrhage, with previous amenorrhea. Three clinical phases can be distinguished.
Asymptomatic according to develop of gestational sac. Subsequently, the patient will start the
symptomatic phase characterized by variable intensity pain. This pain is caused both by
distension of the tubal wall due to gestational sac growth and hematoma coming from
trophoblastic invasion of the wall vessels. Finally in the shock phase, tubal wall rupture
causes bleeding into the peritoneal cavity with peritoneal irritation.
Treatment of ectopic pregnancy: may be medical with methotrexate or surgical.

Laparoscopic approach can be applied, and also salpingostomy or more frequently
salpingectomy.
b) Genital malformations [40,41]
There are multiple malformations of the genital tract. Mostly are asymptomatic and they
have discovered on imaging studies with other aims or sterility studies. However some of
these malformations may be symptomatic.
Imperforate hymen: it is the most common malformation of the vagina. It is

produced by the non-full pipe vagina. They are usually diagnosed at menarche,
because hard painful cycles due to vagina distension by accumulated blood
(hematocolpos). Sometimes accumulated blood may increase also distending the
uterus and the tubes leading to increased pain patient clinic and can be showed as a
palpable mass on examination. Treatment involves cross incision on the hymeneal
membrane.
Vagina double: vaginal walls, is one of the most common congenital malformations.
Vaginal walls can be spread throughout the midline vagina resulting in a double
vagina, or can be partial. In some cases are walls in transverse plane or ring shape.
These may be asymptomatic if they are incomplete but is they are low location often
produce dyspareunia. Sagittal partitions often produce dyspareunia as well. Vaginal
walls hardly cause dysmenorrhea. The treatment, if required, is always surgical.
Cervix malformations: are rare and can occur by atresia, agenesis or aplasia.
Clinically can present as primary amenorrhea with cyclic pain and menstrual. The
treatment is surgical, with cervix perforation and polyethylene tube installation to
prevent re-stenosis.
Uterine partitions: can be variable sizes with partitions in cervix and vagina or
isolated. They become asymptomatic, showed with repeated abortions, prematurity,
infertility or cause dysmenorrhea. Treatment consists of hysteroscopic septum

resection.
c) Pathology of the uterine corpus
Uterine fibroids [42,43,44,45] Common body usually asymptomatic, but may also
show with clinical painful by compression or degeneration.
Fibroids can be splited according to their location in subserosal, intramural and

submucous. Subserosal fibroids are those that appear near the uterus serous causing a
protrusion on its surface. They are usually asymptomatic but if they are large size may show
with compressive symptoms of close organs. In cases where the fibroid is pedunculated,
torsion may occurs causing a sharp pain clinic due to necrosis.
Intramural fibroids are the most common (50-55%), they grow in the thickness of the
myometrium and may increase the uterus size producing irregularities in its wall. They are
usually asymptomatic, but they are big size can cause chronic pain and feel heaviness.
Submucosal fibroids grow into uterine cavity. Rarer than previous ones, they are more
symptomatic. They are often manifested by hemorrhagic syndrome. Sometimes submucosal
myoma has a foreign object on uterus body, which forces contractions, painful for the patient,
in order to expel it. If these contractions come to dilate cervical canal can move fibroid into
the vagina (fibroid delivery).
Fibroids may undergo degenerative changes:
-Atrophy, due to hypo-estrogenic state it comes with menopause. Myoma reduces

size and vascularization. Asymptomatic. It can also occur during treatment GnRH
drug analogues.
-Edema, due o venous stasis within the fibroid.
-Hyaline degeneration: results from replacement of connective tissue by hyaline
material, mostly occurs in the subserosal fibroids.
-Cystic degeneration: is produced by hyaline material liquefaction within fibroid.
-Degeneration-infectious: it is very rare. It occurs almost exclusively in the
submucosal fibroids. It causes intense pain and fever
-Necrosis: is caused by circulatory failure in the fibroid vessels. It could be focal or
diffuse. Manifest with clinical pain more or less pronounced according to the
necrotic area. In cases of fibroid torsion necrosis, pain can be sharp and very intense.
-Fatty degeneration: it is infrequent and asymptomatic.
-Calcification: usually occurs after menopause, may be partial or total and
asymptomatic.
-Sarcomatous degeneration: It is very rare and produces a quick tumor growth with
necrosis areas. It can be characterized microscopically by high cellularity with
nuclear atypias areas.
Treatment of fibroids is mainly surgical, although we must pay special attention to those
asymptomatic or small size ones. Treatment may be hysteroscopic resection in case of
submucous myomas, laparoscopic myomectomy or open in young women with a nous desire
or hysterectomy in cases of women with reproductive met desires, or in those patients with
large uterus with multiple fibroids highly symptomatic.
In selected cases can be treated by embolization and ablation of high-energy ultrasound
(HIFU).
Endometrial polyps
They are benign and occurred through the focal proliferation of endometrium They can
be sessile or pedunculated. They are usually asymptomatic and in cases of producing any
clinical, this use to be bleeding. In some cases the polyp can become larger producing
dysmenorrheal or chronic pain.
Diagnosis is made by hysteroscopy with resection or biopsy sample. Vaginal ultrasound
and sonohysterography may be useful but only allow us to make a suspect diagnosis.
Not all endometrial polyps require treatment. It must be treated symptomatic ones, in
patients with endometrial cancer risk factors, multiple or large (upper than 2 cm) polyps or
patients with infertility.
The endometrial polyp treatment is hysteroscopic resection.
2. Inflamatory
Biochemical mediators of inflammation are powerfull pain stimulators.
Main causes of this type of pain are pelvic infections, particularly pelvic inflammatory
disease, endometriosis and ovarian cyst rupture with release of their contents into the
peritoneal cavity.
a) Pelvic inflammatory disease (PID) [46,47,48,49]
Pelvic inflammatory disease is an entity that includes high-genital tract infections, ie,
endometritis, salpingitis and gynecologic peritonitis.
It is difficult to estimate the incidence of this disease, because in many cases is
asymptomatic and diagnosis is complicated.
Pelvic inflammatory disease is caused by caused by polymicrobial infection. Its origin is
an ascending infection through vagina and cervix to the mucosa of the endometrium and
fallopian tube. These can be acquired through sexual contact or be part of the patient's flora.
The most frequent sexually transmitted microorganisms implicated in PID are Neisseria
gonorrhoeae and Chlamydia trachomatis, endogenous aerobic and anaerobic bacteria and
genital Mycoplasma hominis and Ureaplasma urealyticum, from digestive flora such as
Escherichia. coli or enterococcus; and sometimes from oropharyngeal flora.
Clinical manifestations of pelvic inflammatory disease depends on the degree of infection

and the agent involved. Neisseria gonorrhoeae has a rapid growth cycle that generates a rapid
inflammatory response in the tube, Chlamydia trachomatis presented a slow growth cycle that
requires weeks to generate the same inflammatory response with a extended tissue destruction
and necrotic tissue is a great medium to generate aerobic and anaerobic invasion, and in a
second step infertility and ectopic preganancy. Main symptom of this condition is pain. May
appear as a sharp pain of varying intensity with or without fever. Sometimes it may manifest
as an insidious pain that typically increases during the day and gets worse with sexual
relations.
The diagnosis of this condition is essentially clinical, based on the patient's symptoms
and pelvic examination. The minimum criteria for diagnosis are: pain on cervical motion,
uterine tenderness and adnexal tenderness. Other information as leukorrhea or fever may help
the diagnosis. Laboratory abnormalities such as leukocytosis or elevated PCR will be useful
to support the diagnosis of PID, but not essential. Imaging tests are needed to make a
differential diagnosis with other gynecological or gastrointestinal disorders that present with
lower abdominal pain and to diagnose complications such as pelvic abscess.
The treatment of pelvic inflammatory disease is antibiotic therapy and should be done at
an early stage, empirical, and of a broad spectrum because these are usually polymicrobial
infections. If there are abscesses or peritonitis, surgical treatment is necessary, preferably
laparoscopy, with abscess drainage and washing of the peritoneal cavity.
b) Endometriosis [50,51,52]
Endometriosis is a major cause of chronic pelvic pain. This disease is caused by

endometrial tissue outside the uterus, usually in the pelvis.
The prevalence of endometriosis is complicated to estimate because of the difficulty of
diagnosis. In a study by Eskenazy was found that 4% of asymptomatic women undergoing
laparoscopic tubal ligation had endometriosis, 20% of the women studied for infertility and
24% of the patients studied for pelvic pain. The age range is between 25 and 30 years. It is an
estrogen-dependent disease that mainly appears in women of reproductive age with early
menarche, short menstrual cycles and longer periods.
There are several classifications. The most frequently used in the established by the
American Fertility Society established four stages: minimal, mild, moderate and severe,
considering the size and location of lesions and the presence and characteristics of adhesions.
This classification does not consider the biological activity of the areas . Some patients
have small but very active areas, and therefore highly symptomatic. In contrast some patients
with extensive areas may remain asymptomatic.
There are several etiopathogenic theories that explain the etiology of endometriosis. They
are mainly: the theory of transplantation or dissemination endometrial and metaplastic theory.
The first one includes the theory of retrograde spread through the tubes and blood or
lymphatic spread, which would explain the appearance of endometriotic areas in remote
places such as skin, lungs and brain.
According to the metaplastic theory, endometriotic areas may arise from the
differentiation of embryonic coelomic tissue present in many pelvic and extrapelvic
structures.
Clinically, endometriosis can occur in variable forms. Symptoms may also be confused
with other diseases and are commonly chronic, which makes the diagnosis may be delayed
several years.
Dysmenorrhea, dyspareunia, chronic pelvic pain and pain with ovulation are common in
these patients. On clinical examination we can observe an increase in pelvic tenderness,
presence of a fixed uterus retroflexion, uterosacral ligaments tender and enlarged ovaries by
the presence of endometriomas. In cases in which we suspect endometriosis of rectovaginal
septum, rectal examination may be helpful. All these signs are most pronounced during
menstruation. We must consider that physical examination could be normal.
The mechanisms by which pain symptoms occurs in these patients are hard to explain.
On one hand, the presence of ectopic endometrial tissue into the peritoneum induces a higher
presence of macrophages, which produce an increase of lysosomal enzymes, causing
increased tissue damage and prostaglandins, this will produce chronic pelvic pain. On the
other hand, the rupture of an endometrioma will output its contents into the peritoneal cavity
inducing a chemical peritonitis with significant acute pain. If the output of content occurs
slowly, pain may manifest chronically. Adnexal adhesions and in pouch of Douglas may be
responsible for chronic pain and dyspareunia for the anatomical alterations that produced. In
addition, endometriotic areas can cause painful symptoms due to compression of other
organs, damage in nerve fibers and tissue ischemia.
Diagnosis
After carrying out a detailed clinical history, paying particular attention in the patient's
pain clinic and their relationship or not with the menstrual cycle, we will proceed to the
physical examination, which as explained above can show signs of endometriosis or be
completely normal. Additional tests are transvaginal ultrasound, transrectal ultrasound and
magnetic resonance imaging. With transvaginal ultrasound we can diagnose the presence of
ovarian endometriomas and rupture of fibroids, however it is not useful for diagnosing the
presence of superficial peritoneal areas or pelvic adhesions. Transrectal ultrasound is useful in
cases with suspected endometriosis of rectovaginal septum or uterosacral ligaments. In cases
with suspected of deep endometriosis with intestinal involvement or other pelvic organs can
be assessed the need for an MRI prior to treatment. The MRI is an useful technique to assess
the presence of lesions, their size and involvement of different organs.
The certainty diagnosis of endometriosis is obtained by laparoscopy with biopsy.
Treatment
The treatment of endometriosis should be individualized for each patient depending on

their symptoms, age, extent of disease and presence and duration of infertility
In patients with mild or moderate symptoms who do not want contraception, a good
strategy is to begin with symptomatic treatment with NSAIDs. These drugs do not deal
directly with endometriosis but its antiprostaglandin effect reduce their symptoms,
particularly dysmenorrhea. Cochrane review in 2005 found no evidence that NSAIDs were
useful for the treatment of pain caused by endometriosis.
In patients who want contraception, combined oral contraceptive use has been proposed
as a treatment for endometriosis although there are few studies that support such treatment. In
a meta-analysis by the Cochrane in 2003, only one study met the inclusion criteria proposed.
This treatment would be indicated mainly in young patients because of adverse effects,
especially cardiovascular, in patients over 35-40 years. In one third of patients, painful
symptoms reappear in the 7 pill free days. Have also been reported cases of worsening of
symptoms after three months of treatment.
Progestogens alone would be indicated in the treatment of endometriosis due to two

effects:
Direct antiestrogenic effect and antigonadotropic effect in prolonged use.

Anti-inflammatory effect by acting on the matrix metalloproteinases, a family of
enzymes involved in the phenomenon of invasion of the disease, appear to be
overexpressed in endometriosis injuries. Progesterone inhibits the expression of these
enzymes.
Several studies have demonstrated the efficacy of progestogens in reducing pain in

patients with endometriosis.
In some patients, progesterone resistance is produced, that can be explained by the
endogenous secretion of estradiol in endometriosis
The levonorgestrel-releasing IUD has proven useful in patients with mild endometriosis
decreased dysmenorrhoea 6 months after insertion.
Danazol is an antigonadotropic substance with androgenic and anabolic effect. It
produces an inhibition of the secretion of FSH and LH, with anti-estrogenic effect and
endometrial atrophy. These actions would reduce the symptoms of endometriosis but its
significant adverse effects limit their clinical utility.
GnRH agonists are substances that inhibit the secretion of LH and FSH which produces
an artificial menopausal status and climacteric reversible with endometrial atrophy. A meta-
analysis conducted in 2004 concluded that GnRH analogues are as effective as danazol in the
treatment of endometriosis. The effects of GnRH analogues are appearance of hot flashes,
decreased libido, vaginal dryness. Use them for a long time, can cause urogenital atrophy,
osteopenic and osteoporosis due to anti-estrogenic effect. To avoid these long-term effects, it
is proposed to add to analogues treatment with a combination of progestin and estradiol in
low doses, similar to hormone replacement therapy. This complementary treatment reduces
bone demineralization without clinical adverse effects of endometriosis.
Analogues treatment should be consider in cases of resistance to other treatments and as a
previous treatment to surgery to reduce the size of the implants.
Surgical Treatment
The aim of surgical treatment is to destroy all visible disease, to delay the recurrence of
the disease and destroy adhesions to restore normal anatomy of the pelvis. The way of choice
should be laparoscopic. Since it allows a better visualization of pelvic structures and a
reduction of adhesions and surgical complications.
Recurrence risk is lower when performed extirpation of cysts or endometriotic implants
that when performing ablation or drainage alone.
It is usual the reappearance of symptoms after conservative surgery. It is estimated that
10-20% of treated patients relapse
In patients with treatment-resistant symptoms, it is proposed presacral neurectomy and
laparoscopic ablation of the sacral nerves. Candidates patients for these treatments, may be
carefully selected, because of the risk of postoperative bowel or bladder dysfunction
In older women in which medical and surgery conservative treatment fails can raise
radical hysterectomy and bilateral oophorectomy.
c) Rupture of ovarian cysts
The rupture of an ovarian cyst is a rare complication and usually secondary to a previous
torsion or trauma. The clinic will mainly depend on the nature of the cyst, it can produce mild
pain, which is controlled with analgesia, in cases of moderate-sized functional cysts. In case
of endometriomas, the rupture may cause output of blood to the peritoneum with peritoneal
irritation and pain more pronounced. In some cases, rupture of the cyst can lead to an acute
abdomen and required emergency surgery.
Hemorrhage: Can be intracystic or peritoneal. In cases of intracystic bleeding the patient
had localized pain in the annexed affection, of variable intensity depending on the severity of
bleeding. In many cases the picture is self-limited, controlled with oral or intravenous
analgesia with NSAIDs or weak opioids. In some cases the pain is not controlled , requiring
surgical treatment, consisting of cyst drainage and coagulation of the bleeding vessel.
Intraperitoneal hemorrhage is more symptomatic, patients complain of more intense pain
with peritoneal irritation, nausea and vomiting, and it can cause acute abdomen. In some
cases the bleeding has enough intensity to produce hemodynamic instability, requiring urgent
surgical treatment.
3. Ischemic
The interruption of blood flow to one of the pelvic organs produces tissue necrosis. This
causes an increase in the concentration of degradation metabolites that cause tissue irritation
and pain.
The main causes that produce pain by this mechanism include ovarian torsion, torsion of
subserosal fibroids and ovarian vein thrombosis [53].
a) Ovarian vein thrombosis [54,55]

The ovarian vein thrombosis is a very rare but potentially serious entity, often associated
with other pelvic complications. Most commonly appears associated with post-partum
endometritis. It can also occur as a complication of pelvic surgery and more rarely as a
complication of pelvic inflammatory disease or coinciding with malignant tumors.
It typically presents with pelvic pain of insidious evolution and variable intensity which
decreases with common analgesics
The diagnosis is made by pelvic CT. Ultrasonography usually shows non specific
findings and it can be useful to rule out other pathologies with fever and pelvic pain such as
appendicitis, ovarian torsion or endometritis.
The treatment of ovarian vein thrombosis is anticoagulation and administration of
parenteral antibiotics.
b) Ovarian torsion
Ovarian torsion witch is a frequent complication of adnexal cysts. It occurs in cases of
tumors of medium size, pedunculated and witch is more common in girls and young women
and in pregnant in the first weeks of gestation. Depending on the degree of torsion the
symptoms will vary from mild pelvic pain, slow onset, until acute abdomen. Often the patient
with ovarian torsion presents with pelvic pain of slow onset, which increases with time and
witch is resistant to oral NSAIDs analgesia. Adnexal torsion leads to an increase of free liquid
with a degree of peritoneal irritation that can cause digestive disorders mainly vomiting. On
clinical examination we found abdominal pain with cervical motion pain, and diffuse pelvic
pain with signs of peritoneal irritation. In some cases the adnexal mass is palpable. Vaginal
ultrasound can demonstrate the existence of adnexal mass, with variable amount of free
peritoneal liquid. In cases where the torsion is complete Doppler study of the tumor vessels
show no flow, with normal vascularity in the contralateral annexed.
Treatment of ovarian torsion is surgical laparoscopy, If the compromise is severe, in
some cases oophorectomy will be required.
III. Treatment
The World Health Organization (WHO) analgesic ladder was created in 1986 with the
aim of providing a progressive analgesic treatment in patients with chronic pain. The
specialized treatment of chronic pain requires the use of drugs according to the pain intensity
and effectiveness of the drug. The therapy begins with simple and inexpensive drugs and
progress in treatment to the opioids group, nerve blockers, or surgery until obtain a sufficient
pain relief in the patient.
The pathophysiological mechanisms and symptoms of neuropathic pain are quite
different from nociceptive pain, therefore, the treatment of each of them should be
approached quite differently. In the treatment of neuropathic pain, non-steroidal anti-
inflammatory (NSAIDs), analgesics, antipyretics and opioids drugs appear to have little
therapeutic value, while the most effective drugs for this kind of pain, are the membrane-
stabilizers, anticonvulsants and antidepressants.
Basis on the pathophysiology classification, pelvic pain may be consider as a mixed pain,
hence the need to build a selective analgesic ladder combined the treatment of neurophatic
and chronic pain, this new analgesic ladder consists in three steps and is the guideline for the
pain management56:
1. Therapy for Pelvic and Perineal Pain Step One (Mild and Moderate Pain)
1.1. Therapy for Chronic Pain Step One
a) Minor analgesics: anti-inflammatory (NSAIDs) and antipyretics, associated or not,

with adjuvants as antiepileptic drugs, antidepressants, hypnotics or corticosteroids, in order to
increase the analgesic efficacy or simply treat the symptoms that exacerbate pain.
Antipyretics: aspirin, paracetamol, combined with free analgesic periods.

Non steroidal anti-inflammatory drugs (NSAIDs): Use in the case of failure with the
previous group, provides a relief of symptoms and for the inflammatory process.
Example: Ibuprofen.
b) Rehabilitation: Reduces the pain and improves the functionality.
Exercise programs: light physical exercise as walking, stimulates the release of

endorphins, promotes flexibility, strength and reduces stress. The exercise
strengthens muscles and improves the overloaded muscle cause of pain, associated
with a training in weight control.
Rehabilitation therapy: Physical therapy, relaxation techniques, stretching or pull
exercises muscle, the heat or cold therapy, biofeedback, should be initiated early and
combined with oral drugs.
Transcutaneous electrical stimulation (TENS): The application of electric pulses
to the nerves endings in the areas of pain, are made with the aim to interrupt the
transmission of pain and stimulate the release of endorphins
c) Psychological support: the aims are to solve problems concerning dysfunctional

emotions, behaviors and cognitions caused by pain
Cognitive behavioral therapy: Chronic pain causes a great psychological impact,

tolerance and patient response to pain depends on many factors as personality,
culture and previous experiences.
1.2. Neuropathic Pain Therapy Step One
A. Care of the Vulva
1. Increase the welfare of patient [57]
Avoiding substances that cause vulvar irritation such alcohol, irritants, perfumes,
dyes, detergents, douche.
Application of ice packs or cold for local pain control (for periods of more than 20
minutes each time) or baths, wear loose clothing and underwear cotton 100%.
Hygiene: Use mild soap to the skin and water in the vulva, drying the external
genitalia with small touches without rubbing.
Use low-oxalate diet and nutritional supplement of calcium citrate [58].
2. Maintain skin moisture and improve its barrier function
After intimate hygiene, apply emollients without preservatives, such as vegetable oil or
vaseline, without excipients.
3. Sexual counseling59
Psychological and sex therapy: advice about sex life.

Use local anesthesic before sex.
Contact with organizations to provide education to patient and their families, in order
to avoid feelings of isolation in women who may experience vulvar pain.
B. Topical Treatment
1. Local anesthetics: The topical anaesthetics, block the transmission of afferent C fibers
and inhibit the irritable nociceptors caused by repeated exposure, thus reducing the feedback
amplification of pain. The most widely used agent is lidocaine: 2% jelly or 5% ointment,
employing 20 minutes before intercourse. Currently there is a new presentation of Lidocaine
5% patch thats apply up to three patches, only once for up to 12 hours within a 24-hour
period in a intact skin to cover the most painful area. There is no experience in vulvodynia
treatment. Some studies60 have been reported in women with vestibulodynia a 40%
improvement in their sexual relationships when applying nightly a topical anesthesic
lidocaine 5% during 7 weeks, six months later a 86% of patients who stopped the treatment
showed a relief of symptoms and improvement in the ability to have sex. Ointments are
usually better tolerated than creams. Benzocaine should not be used because it produces
contact dermatitis.
2. Capsaicin: Is a substance that activates axons A-A of sensitive neurons and

unmyelinated C fibers. The mechanism of action is based on the desensitization caused by an
acute reaction mediated by neuropeptides (substance P). It is useful for treating neurological
and inflammatory disorders, that cause chronic pain and those disease which have increased
levels of substance P. Steinberg et al. reported in patients with vestibulodynia, that local daily
application for 20 minutes of 0.025% capsaicin cream for 12 weeks, reduced significantly the
discomfort and increase the frequency of sexual intercourse61. Currently there is a new
presentation of capsaicin 8% patch, is left on the painful area for 30-60 minutes, after which
the patch is removed and the skin is cleansed. This may be repeated every 12 weeks as
necessary. There is no experience in vulvodynia treatment.
3. Other topical treatments
Nitroglycerin: Topical nitroglycerin is an effective and safe treatment, that causes

temporary relief of symptoms in patients with vulvar pain or introital dyspareunia. Women
who completed the treatment experienced a significant improvement in their overall pain and
pain with sexual activity. The most important adverse effect is the headache, which is cause
of disruption of the treatment62.
Estrogen: It can be an effective treatment for improving symptoms in women with local
estrogen deficiency. The application of estrogen cream in the affected areas for 1-2 months
must be accompanied by measures such avoid stimuli and sexual relation cause of pain.
Lubricants and interferon creams
C. Oral Therapy
In the oral treatment of patients with neuropathic pain, is involved the use of antiepileptic
(AEDs) and/or antidepressants, alone or in combination. In case of association with a
nociceptive pain component, must be attached an NSAID. Some authors place the tramadol as
a specific drug.
1. Antidepressants [63,64,65]
a) Amitriptiline: is a tricyclic antidepressants (TCA). TCA is the best choice for treating
the located symptoms of pain in neuropathic patients, the complete response to treatment in
patients with different degrees of vulvodynia is 47%.
Dosage
Initial oral dose is between 5 and 25 mg at night and increased by 10 to 25 mg
weekly. The period provided for the control of symptoms is 4 weeks.
Maintenance dose: maximum 150 mg per day orally in single or divided doses.
Dose increases should be made gradually. ECG, blood pressure, and heart rate
monitoring is recommended for patients receiving high doses. The most common adverse
effects are sedation, lethargy, weakness, dizziness, dry mouth, visual disturbances, tinnitus,
palpitations. To reduce the adverse effects is to start with a single dose at night and gradually
increase the dose weekly. In case of sedation that will incapacitate the patient can be replaced
by desipramine or nortriptytine.
b) Others antidepressants [66,67]: Venlafaxine or duloxetine are a selective serotonin

reuptake inhibitor (SSRI). Venlafaxine have been used for pain control in vulvodynia but the
use of duloxetine in neuropathic pain management are limited, Some studies confirms that 60
mg once or twice daily is effective and safe in the management of some neuropathic pain
disorders.
2. Anticonvulsants: Similarities between the pathophysiologic phenomena observed in

some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the
symptomatic management of neuropathic pain. Evidence supporting the efficacy of
anticonvulsants in treatment of such pain is evolving.
a) Gabapentin [68,69]: is a structural analogue of the neurotransmitter gamma-
aminobutyric acid (GABA), is an antiepileptic drug with an unknown mechanism of action
apparently dissimilar to that of other antiepileptic agents, and possessing some desirable
pharmacokinetic traits for neuropathic pain relief. Gabapentin is indicated when there is no
response to high doses of tricyclic antidepressants or no tolerance to treatment. Ben-David
and Friedman have reported a partial or complete efficacy in women with vulvar pain was
82%.
Dosage
Initial dose: 300 mg orally on day one, 300 mg orally twice a day on day two, then
300 mg orally 3 times a day on day three. The dose may be titrated up as needed for
pain relief to a daily dose of 1800 mg.
Maintenance dose: 900 to 1800 mg orally in 3 divided doses. Efficacy was
demonstrated in clinical studies over a range of 1800 mg/day to 3600 mg/day.
However, no additional benefit was demonstrated from the use of doses over 1800
mg/day
The painful relief response and tolerance to adverse effects is not evident for even 3 to 8
weeks of Gabapentin use. The most frequently adverse effects are drowsiness, dizziness,
ataxia and dosage adjustment are needed in patients with renal insufficiency.
b) Pregabalin [70]: is an anticonvulsant drug used for neuropathic pain. Additionally is a

efficaciously treatment in partial seizures with or without secondary generalization,
fibromyalgia and generalized anxiety disorder. Pregabalin is associated with decreased sleep
interference and significant improvements in quality of life.
Dosage
Initial dose: In our experience the starting dose are 25 mg two times a day during one
week, the adverse effects of pregabalin are more important than gabapentin. The
starting dosage with 75 mg every 12 hours may be provided adverse effects on
central nervous system. The dose may be increased to 100 mg 3 times a day within 1
week based on efficacy and tolerability.
Maximum dose: Patients who do not experience sufficient pain relief following 2 to
4 weeks of treatment with 300 mg/day and who are able to tolerate pregabalin, may
be treated with up to 300 mg 2 times a day or 200 mg 3 times a day. Due to the dose-
dependent adverse effects and the higher rate of treatment discontinuation due to
adverse events, dosing above 300 mg/day should be reserved only for those patients
who have ongoing pain and are tolerating 300 mg daily.
c) Carbamazepin: was the first of drugs of this class studied in clinical trials and has
been used for treatment of neuropathic pain. FDA approval and clinical trial data support its
use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are
less convincing. Its use is reserved for patients with resistant to treatment. This drug needs
monitoring of liver function but has shown the best results in the treatment of some
neuropathic pains.
Dosage
Initial dose: 100 mg orally twice a day (immediate or extended release). May
increase by up to 200 mg/day using increments of 100 mg every 12 hours (immediate
or extended release), only as needed to achieve freedom from pain. Do not exceed
1200 mg/ day.
Maintenance dose: 400 to 800 mg/day. Some patients may be maintained on as little
as 200 mg/day while others may require as much as 1200 mg/day. At least once
every 3 months throughout the treatment period, attempts should be made to reduce
the dose to the minimum effective level or to discontinue the drug.
d) Other anticonvulsants: including valproate, topiramate, and tiagabine, have also been
under investigation.
D. Biofeedback and Physical Therapy [71,72,73,74]:

These rehabilitation techniques can be used to treat the localized or generalized vulvar
pain and are also useful for the treatment of vaginismus. Patients with vulvodynia have an
increased tone in pelvic floor muscles, spastic contractions and general weakness caused of
myofascial syndromes. 71% of patients with chronic vulvar pain treated with Physical therapy
showed a improvement higher than 50% on overall symptoms, 62% in sexual activity and
50% in the quality of life.
The intravaginal electrical stimulation, are used to treat the pelvic floor muscle spam,
some authors reported a 79% of returned to sexual activity.
2. Therapy for Pelvic and Perineal Pain Step Two (Moderate-Severe

Pain and Refractory to Treatment Level One):
2.1. Therapy for Chronic Pain Step Two

a) Weak opioids: tramadol or codeine, associated or not with NSAIDs and adjuvants, if
are necessary. Opioids are effective in the relieving of the intense pain but have adverse
effects such as drowsiness, constipation, risk of addiction.
b) Nerve Block:
Local anesthetic or corticosteroids infiltration of the affected nerve. The blocking
have a temporary effect but can reduce the inflammatory component that causes
nerve irritation and pain
Neurolysis: the objective is to prevent the nerve send pain signals to the brain, for it,
is injected alcohol or phenol around the nerve affected, in order to destroy and
disrupt the nerve function. The relief of pain symptoms occur for weeks or months.
Thermal therapy: the temperature is used to interrupt the nerve's ability to transmit
pain signals
Cryoanalgesia: the application of cold to the nerve, depending on the extension and
intensity of exposure, causes a minimal nerve damage with a sensory deficit for
weeks or a complete loss of sensory function and decreased motor function.
Radio frequency: is the application of high frequency energy to produce heat and
thermal coagulation of the affected nerve. The treatment is selective, which reduces
the risk of nerve damage or peripheral tissues and provide pain relief for a period
exceeding one year.
2.2. Neuropathic Pain Therapy Step Two
A. Oral Therapy
In the second step of oral neuropathic treatment the anticonvulsants and/or
antidepressants with weak opioids as tramadol or codeine can be combined. In case of mixed
pain, must be combined with NSAIDs.
B- Local Infiltration
a) Local anesthetic or/and corticosteroids infiltration: Local anaesthetic nerve blocks

can be performed by different approaches: caudal epidural block, transvaginal pudendal or
transperineal vestibular infiltrations, the approach can be done by finger-controlled,

vaginal ultrasound, or transgluteal under scanner. The agent injected can be an
anaesthetics or corticosteroids alone or combined, in the sensitive area or peripheral nerve
route. Depot corticosteroids combined with local anaesthetics, block the afferent pathway of
pain and the steroid the inflammatory response.
Dosage
1.- Caudal epidural block: 10 mL of 0.2% ropivacaine through the sacral coccygeal
hiatus
2.- Transvaginal pudendal infiltration: 5 mL of 0.25% bupivocaine for each side or 10
to 15 cc of ropivacaine 7.5 mg/mL75
3,- Transperineal vestibular infiltration:
10 mL of 0.25% bupivocaine delivered into the vestibule, at the 6 oclock position,

then directing the needle to the right and left
Lidocaine 1% and 2 cc of betamethasone [76,77]
No more than 40 mg of triamcinolone acetonide 0.1% monthly combined with 0,25%
of bupivacaine in large area and 0,5% in small area in three or four trials [78].
Methylprednisolone and lidocaine injected into the vulvar vestibule once a week for
three weeks at decreasing doses: 1ml, 0.5ml, 0.3 ml [79]
b) Intralesional interferon alpha (INF-): Multifunctional immunomodulatory

cytokine with wide effects on viral, malignant, angiogenic, allergic, inflammatory or fibrotic
disease. It is an important regulator of growth and differentiation, affecting cellular
communication and immunologic control. Recent data suggest its properties as anti-
inflammatory drug. The role in perineal pain is when there is no response to treatment.
Dosage
Based in HPV treatment we use a INF- injection of 1MU 3 times/week for 4 weeks in
the vestibular periphery. The most common adverse effects are flu-like symptoms. Marinoff
et al reported a 49% with partial or complete improvement. [80,81]
c) Botulinum toxin [82,83,84]: There is evidence supporting the use of both botulinum
toxin type A and type B in the treatment of myofascial pain syndrome. The injection of 5.000
to 12.500 units of botulinum toxin type B or 150 units of type A have been reported in the
literature for the management of myofascial pain syndrome. No single technique is
universally accepted, the procedures most commonly used includes digital localization of the
muscle, with ultrasounds or electromyographic guidance. An excellent efficacy of 90% have
been published with a low rate of adverse effects such dry mouth.
3. Therapy for Pelvic and Perineal Pain Step Three (Severe Pain
Refractory to Treatment Level One and Two)
3.1. Therapy for Chronic Pain Step Three
Chronic pain could be refractory to standard therapies level one or two. In that case must
be use advanced treatments.
a) Strong opioids: morphine and derivatives, combined with NSAIDs and adjuvants, if
necessary.
Implantable drug pumps: drugs can be introduce directly into the cerebrospinal fluid
trough the intrathecal space of the spinal cord. This technique allows the use of opioids
analgesics at lower doses than oral or transdermal therapy, reducing the adverse effects.
b) Neurostimulation: the stimulation of the spinal cord is perform using a low levels of
electrical impulses in order to block the pain signals to the brain. This therapy replaces the
symptoms of pain in the affected area turning it in a more pleasant sensation85. Currently we
have new stimulators, more effective and easier to apply.
c) Surgery: the surgical treatment for chronic pain can be directed to repairing an
anatomical defect caused by disease, injury or can be oriented to interrupt the transmission of
pain signals. Surgery present more risk than non-invasive procedures.
Neuroablation: a surgical technique aimed at the permanent destruction of neural tissue

involved in chronic pain transmission. The neuroablative procedures may be have only
temporary results because neural tissue can develop new neural pathways for the pain
transmission. The surgical procedures are as follow:
Cordotomy: surgical resection of a segment of the spinal cord.

Rhizotomy: selective destruction of a nerve close to the spinal cord.
Thalamotomy and pallidotomy: radio frequency is used for the specific destruction
of deep brain areas. This technique can cause sensory or motor dysfunction in a
normal area (without affecting the pain).
3.2. Neuropathic Pain Therapy Step Three

A. Oral Therapy86
In these step is administered the anticonvulsants and/or antidepressants with strong
opioids as morphine, oxycodone, transdermal fentanyl or buprenorphine. If we suspect a
nociceptive pain we associate also an NSAID.
Because of its dual mechanism of action the best option in neuropathic pain are
oxycodone or methadone
B. Surgery [88,89,90]: In the case that vestibulodynia symptoms are severe, for a longer
period of time, and do not respond to medical treatment, the surgical indication can be
considered. Unfortunately, one effective surgical treatment for neurologic pain cannot be used
in vulvar pain syndrome because cutting the pudendal nerve causing the problem that playing
a role in the bladder control. It is unknown how much tissue must be removed, but in any case
should be as little as possible, therefore it is important in the operating room before the
patient is anesthetized identify and delimit the areas of pain, called excision zone. Surgery
should be limited to the extent necessary to relieve the symptoms, the efficacy of surgery are
40-89% but consider that approximately 10% of women may experience worsening of
symptoms after surgery [87]. The extent of the excision, classifies the surgical technique in:
Table 6. Analgesic ladder in pelvic pain: guideline for the pain management [56]
1step 2step 3step

Minor analgesics Weak opioids Strong opioids
NSAID Tramadol Morphine
Antipyretic Codeine Oxycodone,
Transdermal fentanyl
Buprenorphine.
Rehabilitation Nerve block Neurostimulation
Exercise programs Local infiltaraion
Rehabilitation therapy Anesthetic or/and
Physical therapy corticosteroids
Biofeedback Interferon alpha
TENS Botulinum toxin
Neurolysis
Thermal therapy:
Cryoanalgesia
Radio frequency
Psychological support Surgery: Neuroablation
Cognitive therapy Cordotomy
Rhizotomy.
Thalamotomy, pallidotomy
Vulvar care Surgery: Vulvar pain
Welfare of patient Vestibuloplasty
Maintain skin moisture Vestibulectomy
Sexual counseling Perineoplasty
Surgery pudendal nerve entrapment
Topical therapy
Local anesthetics
Capsaicin
Nitroglycerin
Estrogen
Lubricants
Interferon
Oral therapy
Antidepressants
Amitriptiline
Venlafaxine
Duloxetine
Anticonvulsants
Gabapentin
Pregabalin
Carbamazepine
1. Vestibuloplasty: Is the local excision of a localized painful area without vaginal

advancement or a procedure to denervate the sensitive vestibular tissue, cutting the pudendal
nerve branches that give sensitivity to the vestibule, without excision of tissue in which pain
occurs. Bornstein et al. in 1995 in a prospective randomized study, evaluated the effectiveness
of vestibuloplasty in the treatment of severe vulvar pain syndrome, obtaining an unacceptable
results and concluded that vestibuloplasty fails because the innervation disturbances are not
the main cause of the syndrome.
2. Vestibulectomy: Woodruff and Parmley in 1983 described the resection of hymen and
vestibule with mobilization of the lower part of the vagina with the objective of eliminate the
painful area. Patients undergo testing with a cotton swab before anesthesia while in the
operating room to outline the areas of pain. The procedure consist in the excision of the entire
vestibule under the urethra to the perineum, including the hymen and 2-3 cm of vaginal
epithelium. The overall rates of success are between 60-94% (Gaun et al reported 90% of
symptoms relief caused by vestibulodynia).
3. Perineoplasty: entails combination of vestibulectomy and removal of tissue on the

perineum, usually terminating just above the anal orifice.
Surgical complications: Bleeding, bruising, infections, surgical wound dehiscence, cyst

in the Bartholin glands, weakness of anal sphincter, vaginismus, vaginal stenosis,
lubrification decreased and recurrent pain. Disadvantages: The removal of glands necessary
for sexual lubrication, the scarring and a possible recurrence at 6 months. The surgical
efficacy of these techniques decreased in long-term studies (>6 months).
4. Surgery for pudendal nerve entrapment: The role of surgery is to decompress the
pudendal nerve similar to carpal syndrome surgery. Four different approaches are described:
a) The transgluteal approach91 involves a gluteal incision overlying the ischial
tuberosity. The sacrotuberous and sacrospinous ligament are identified at the level of the
ischial spine. The overlying fascial of Alcocks Canal is also incised as is the remnants of the
falciform process if necessary. The nerve is then transposed in front of the ischial spine.
Advantage: good access and visualization of all areas of possible pudendal entrapment.
Disadvantages: the necessary sacrificing of both the sacrospinous and sacrotuberous
ligament in some patients. There is a modified technique in some patients so that the
sacrotuberous ligament is not compromised. Patients with sacroiliac joint dysfunction, needs
a intact sacrotuberous ligament.
b) The transischiorectal approach [92] involves a vertical vaginal incision to enter in
the pararectal space. The rectum is retracted medially and the sacrospinous ligament is
identified and divided progressively. In case of falciform process the sacrotuberous ligament
is partially divided. The nerve is testing and digitally explore in the canal caudally to ensure a
completely free status.
Advantage: good access to all of the surgically areas of entrapment. The procedure
avoids a direct manipulation of the nerve, thus, reducing neurological complications and the
complete sectioning of the sacrotuberous ligament.
Disadvantages include a smaller field of vision during the procedure. Operators must be
familiar with the vaginal approach
c) The transperineal approach [93] involves a vertical para-anal incision to enter into
the ischiorectal fossa, the inferior rectal nerve is identified then traced back to Alcocks
Canal. Alcocks Canal is then opened
Disadvantages: This technique is limited by its small area of exposure and incomplete
access to all the possible areas of entrapment (the clamp between the sacrospinous and
sacrotuberous ligaments).
A modification of the technique by a opening in the fascia (fasciotomy) enables the
passage of one finger into the abdomen which is largely sufficient to free the nerve, with this
modified technique, all areas of entrapment can be addressed with a minimally invasive
procedure and without cutting any ligaments.
d) The laparoscopic approach94 was described by Nieves et al. in 2005.
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Chapter II
Local Use of Electrophonophoresis in

the Treatment of Patients with
Immunologically Based
Neuro-Vertebral Conflicts
Andrzej Dyszkiewicz*
Laboratory of Biotechnology, LABIOT, Cieszyn, Poland
Specialist Physiotherapy and Rheumatology Clinic for Outpatients
"VIS" Cieszyn, Poland
Physiotherapy Institute, University of Technology Opole, Poland
Abstract
This study is a continuation of research on a variety of destructive processes of the
disc, which lead to neuro-vertebral conflict. The cited literature features in particular a
thread on immunological events accompanying disc disease as well as the issue of
treating such disorders.
The aim of this work was to try to answer the question whether the Polish method of
electrophonophoresis used to infuse medicine with confirmed localized
immunomodulatory and analgesic characteristics will result in a longer lasting clinical
effect than after using NSAIDS.
The results of subjective pain feature tests (VAS scale) and changes in the
concentrations of immune complexes (CICs) have been demonstrated using relative
indicators. Laseques test and electro-sensory (HFA and ESTT) test results have been
presented as asymmetry indicators on a common ratio scale.
For the purposes of the research, the following groups were selected: a group (0) of
30 healthy subjects and a group in the age range 30-55 years, suffering from lower back
pain, who were diagnosed, first through X-ray examinations and then through CT as
* Contact information: e-mail: andrzej@labio.com.pl;PhD Andrzej Dyszkiewicz, 43-400 Cieszyn ul. Godzikw 2,
Poland
46 Andrzej Dyszkiewicz
having a hypodensive cyst with a surface area of W(c) > 20% in the cross-section of the
interevertebral disc as well as an increased level of immunological complexes. These
patients were divided into 8 groups (A,A1,B,B1,C,C1,D,D1) and treated using levamisol,
profenid, borovinum and chloroquine by means of traditional iontophoresis (E) and
electrophonophoresis (EF).
The tests showed that the average concentrations of immune CIC complexes in
groups A,A1,B,B1,C,C1,D,D1 of patients with an inter-vertebral disc hypodensive cyst in
the areas of L4/5 or L5/S1 are significantly increased compared to people from control
group (0) and the ELT and ESTT index values show significantly increased asymmetry
compared to patients from control group (0).
The electrophonophoresis (EF) method has decreased pain-induced discomfort
according to the VAS scale and has led to an increase of ELT and ESTT symmetry
parameters in a clearer and statistically more significant manner than after using
iontophoresis (E). Treatment, especially in the case of electrophonophoresis (EF) has
decreased VAS scale based pain-induced discomfort and increased the ELT and ESTT
symmetry parameters, especially after using levamisol and chloroquine, leading most
probably to a decrease of the immunological activity of the cysts, the non-specific marker
of which can be the normalisation in the concentration of circulating immune complexes
(USTI). This phenomenon, despite its methodological non-specificity, is very significant
statistically and does not disappear once pain is relieved following the administration of
profenid.
Keywords: lumbar disc, inflammation cyst, percutaneous electrophonophoresis,

immunomodulators.
Introduction
Pain in the lumber area of the spine may result from dislocation of the inter-vertebral disc
or from a disorder of the spine's biomechanics [5]. After birth, the disc is of a jelly-like
structure and has some cartiladge and fibrous elements, which ensure mechanical durability.
Pulsating pressure on the intervertebral disc alters the volume area of the intercellular cavities
and the pressure pressing on the tissue fluid of the vertebral body. When the pressure rises,
it's penetration into the intercellular cavity of the cartiladge rises, when the pressure falls it
retracts[1]. A pulsating movement of the tissue fluid enables an oxygen substrate exchange to
take place between the blood vessels and the blood supply deprived cartiladge. Such a
nucleus pulposus, positioned between two incompressible parts - vertebral bodies, functions
like a hydraulic absorber. Loads borne along the spines axis lead to compression of the
colloid. The pressure is distributed in the colloid's bubble-like network structure and is
absorbed by forces interacting between ions. In case of heavy loads, the flexibility of the
colloid's network is exhausted, leading to a breaking of the electrostatic connections of ions
hydrating the structure of the colloidal protein and mucopolysaccharids, thus causing water to
be squeezed out of the colloid's structure. This is in turn causes the volume of the colloid to
decrease, leading to its stratification and lowering of the intervertebral size. In a healthy state,
once force is removed, the colloid rehydrates and assumes its initial volume. The spine has
very high capability in carrying even the heaviest pulsating loads, because breaks made
between each force compressing the nucleus allow for osmotic relaxation and recirculation of
the tissue fluid[7][8].
Local Use of Electrophonophoresis in the Treatment of Patients 47
Many disease-related processes as well as malnourishment lead to a fall in the electric

charge of the colloid and proportionally lower the degree of its hydrophilicity. This leads to a
lowering of the baseline volume of the disc and a decrease in the interbody size, which in turn
causes the interbody ligaments to loosen and increases the flaccidity of the bodies [32].
According to many researchers, the development of an intervertebral disc cyst (which is often
the focal point of such a reaction) causes a shift of the loads onto a structurally unprepared
vertebral arch and is one of the causes of pain and overload proliferation in intervertebral
joints and in the spinal ligaments [10][11]. Overload as well as the related extravasion into the
cartilage leads to secondary, inflammatory reparational reactions, whose aim is to decrease
the flaccidity of the interbody connection [55][56]. The following stage in intervertebral disc
disease is gradual cracking of subsequent layers of the annulus fibrosus and the formation of
hernia where the lowest mechanical resistance is encountered [51]. Tearing of the annulus
fibrosus lacking a blood supply and pressure on the ligamentum longitudinal posterius
equipped with a vascularized sac, initiates a reparational process free of any contact between
the immune system and the disc [27]. During the first stage, engorgement, cartilage tissue
proliferation and fibrous ligamental overgrowth occur, and if the bodies are not effectively
immobilized, further ossification of the ligaments takes place leading to the formation of
ostephytes and syndesmophytes [35]. The standard understanding of pain generation in
neurovertebral conflicts, where only the mechanical factor is taken into consideration, is still
prevalent among many doctors [43]. Many test results however, show that the degeneration
mechanism of an intervertebral disc is much more complex. It is worth noting, that
developing vascular clusters direct the migration of lymphocytes, macrophages and precursor
cells for fibroblasts, which, by producing collagen, replenish the loss [44]. Constant
penetration of the body by immune surveillance cells continually verifies cells and systems
based on an HLA-DR antigen analysis. Contact of a tissue, which has been isolated in the
annulus fibrosus for many years since early childhood, with immune surveillance cells, can
result in one of two scenarios: - the surveillance cells may accept the tissue, or in the case of a
malfunctioning immunological memory, the cells may reject the tissue and launch an entire
array of autoimmunological reactions, aiming to destroy and eliminate the tissue, which has
been deemed foreign [15][57]. Immunological reactions can significantly accelerate the
degenerative processes of the micellar network structure of the disc, hampering substrate
exchange with the vascularized tissues and initiating changes in the functioning of metabolic
and enzymatic pathways [61]. Colloid elasticity alterations, which appear as a result of these
processes, lead to a flaccidity of the ligaments and increased bulging of the nucleus pulposus,
which is a source of conflict with the nervous tissue [62][63]. In such a situation, the
application of non-steroid anti-inflammatory drugs takes on a different meaning. Their
painkilling properties may contribute to the local inhibition of an inflammatory reaction.
Considering the encouraging effects of the little invasive treatment initiated by the IDET
method, trials involving the percutaneous treatment of inflammatory and degenerative
processes affecting the disc have been started, the aim of which is to extend the longevity of
the colloid. In situations, where reconstruction is impossible, chemonucleolysis of the colloid
has proven to be effective, which in later stages may be replaced by an elastomer.
Increasingly more is being said about the invertebral disc in cases where shortly after the
resection of a hernial sac, which had been pressing on a nerve, intensive rest pains are felt,
accompanied by the formation of inflammation points and symptoms of meninges'
ossification, which, unfortunately, lead to low back pain and serious deterioration of
motosensory functions [13][14][38][39].
Neurovertebral conflict leads to pain caused by focal, mechanical pressure on the rootlets
in intervertebral canals or nerves in the spinal duct. Its symptomatology is quite characteristic,
and is akin to the characteristic area of skin dermatomes. In addition, both the beginning,
peripheralization of the pain during exacerbation as well as centralisation during remission is
relatively easy to define and verify by the patient and doctor. Pain is often accompanied by a
dysfunction of the touch and temperature receptors of the skin. Discomfort resulting from
isthmus canalis spinalis syndrome, which appears during extensive swelling or inflammatory
proliferation of the spinal duct tissues, is mainly recorded by the spines own nerves, which
have the structure of a disseminated neural network, and send blurred sensory responses,
which are much more difficult to locate. In such a situation, the patient points to a general,
little precise, very heterogenous area adhering locally to the spine. It is much more difficult
for the patient to make a precise determination of where the pain is located, nor can he
provide a quantative description of its parameters.
Drug Activity
The working of drugs in the body depends on the biological activity of the permeating
substances, the efficiency of the circulatory systems absorption, the penetration rate into the
disease stricken area as well as the efficiency of the disposal mechanisms which utilize the
urinary and digestive systems as well as the skin. The key role in the action mechanisms of
most pharmacological substances is played by the primary substance contained in the
administered drug form. Such chemical compounds can be administered orally, parentarally
and percutaneously by e.g. iontophoresis or baroinjection. However there are drugs whose
primary forms do not have any biological functions and are obtained only after
biotransformation in the microsomal system of the liver. One such drug is levamisol, i.e.
2,3,5,6 tetrahydro-6-phenylimidazo 2,1-b thiazole, which undergoes enzymatic degradation
into more significant derivatives: R9280, R43037, R45714, R66003, R92535, R8418,
R43837, R9313[26].
Administering the drug in the form of iontophoresis in a stable electric field will lead to
an incomplete biological effect caused by poor permeation and ineffective dermal and
subdermal biotransformation in a stable electric field.
As long ago as in the 60s, attention was drawn to the fact that many chemical reactions
requiring catalysts and high temperatures or enzymes, proceed at room temperature in an
ultrasonic field. These premises were used for the construction of a chamber for
electrophoresis which later proved the possibility for modifying the structure of methyl blue
and levamisol hydrochloride. The above research results were used for preparing a universal
system for the non-enzymatic modification of chemical compounds and percutaneously
administered drugs, which used the interference of alternating electric and magnetic fields as
well as laser beams and ultrasounds to activate selected chemical substances in doses
dedicated for percutaneous treatment.
In the electrophonophoresis method the surface of the skin is affected by an electric
current gradient, which supplies the dissociated ionic particles with a kinematic stimulus
directed towards the inside of the tissue, while in the meantime the ultrasound wave
vibrations, depending on the frequency used, increase the diameters of intercellular pores,
ionic canals and sweat gland orifices which play a distinct role in the permeation of drugs
through the skin. Another, not less significant effect of high frequency mechanical vibrations
on the particles of poorly polarising drugs (e.g. etheric oils) is a relaxational destabilization of
atomic bindings leading to the creation of electrically charged short-lived dipoles. This
strongly influences the electrokinetic potential and as a result the activity of the drugs
particle [26][24].
The key role in the action mechanisms of most drugs is played by the primary substance
contained in the administered drug form, and it is especially important whether it is capable to
act alone directly after administration or if it requires biotransformation (e.g. in the
microsomal system of the liver). This is a key factor in determining whether the drug should
be administered using iontophoresis of phonophoresis. Many laboratory drugs (e.g. levamisol,
etheric oils, terpenes) would be desirable in local therapy, however, due to the strong causal
effects of the products of their biotransformation and poor absorption into disease stricken
areas not to mention their toxic impact on other organs, the risk of using oral therapy in such
cases is significantly high. Unfortunately, direct and local administration of such drugs in
their primary forms by iontophoresis does not lead to an effective local biotransformation nor
to desirable biological effects. Since the 1960s of the previous century world literature has
been familiar with processes from the so-called ultra-sound chemistry, which forces the
catalytic disintegration of rings in aromatic compounds, or the separation of functional groups
blocking for instance the biological activity of a drug. An adaptation of this to the medical
world has been the electrophonophoresis head, where cavitational microvesicles filled with
heated gas separated from the drug-containing gel form within the drug chamber as a result of
applying ultrasounds and an electric field with regulated frequency, power and modulation
parameters. Diffusion as well as electrostatic and electrochemical phenomena lead to the
adherence of the drug to the vesicles, and the resulting change in the special structure and
temperature can lead to the disintegration of particle bindings with the smallest energy. The
key parameters here are the size of the vesicle, its temperature and vibration frequency. A
strong side thus of the electrophonophoresis head is its power to quickly transform drugs to
an active form on the skins surface right before it enters the body, as the specifically shaped
ultrasound and electric fields lead to the disintegration or dislocation of particular bindings of
many organic compounds, including levamisol, in a similar way to enzymatic catalysis. This
provides us with the technical power to control the disintegration of inactive initial
compounds into structurally changed derivatives, which only in such a form can have any
determined biological effect [16][17][18][19][20][22].
The Aim of the Work

In previous research, the local anesthetic and antiproliferational abilities of levamisol [22]
were proven by achieving good results in percutaneous knee inflammation treatment as well
as in sacroiliac and inter-vertebral disc cyst healing [16][17][23][24]. In the work shown
above, we assessed the influence of chloroquine and borovinum comparing them to
levamisol and profenid in the course of treating low-back pain complexes. In the tests carried
out, clear features of inter-vertebral disc hernia don't appear, however hypodensive areas do.
We've asked some research questions:
1. Are the values of the UTSI standard upper limit indicator, defining the concentration
of the CIC immune complexes in groups A1,A2,B1,B2,C1,C2,D1,D2 comprising
patients with inter-vertebral disc hypodensive cyst > 20% of the L4/5 or L5/S1 cross-
section surface area significantly higher than in patients from the control group (0)?
2. Do the HFA and ESTT indicator values in groups A1,A2,B1,B2,C1,C2,D1,D2 of
patients with L4/5 or L5/S1 inter-vertebral hypodensive cyst indicate statistically
more significant asymmetry than in patients from the control group (0)?
3. Does percutaneous electrophonoretic (EF) treatment decrease pain discomfort and
lead to a normalisation of the HFA and ESTT parameters more significantly than
after ionophoretic treatment (E)?
4. Is a normalisation of the VAS, HFA, ESTT and USTI parameters and a varied degree
of pain relief achieved depending on the use of various medicines such as levamisol,
chloroquine, borovinum and profenid in percutaneous treatment?
Materials and Methods
Groups of Patients, Inclusion Criteria
Figure 1. 3D presentation of a cyst section (P1) on the background of an inter-vertebral disc section
(P2) allows for the W(c) indicator to be established. A W(c) value of < 20% is a criterium for admitting
the patient to a test group.
Table 1 Averaged estimation results of patients in groups A1, A2, B1, B2, C1, C2, D1,
D2 given for : (A) SFTR measurements as averaged asymmetry indicators (P/L), (B)
neurological examination as major trend (R<L) or (R>L), (C) for pains descriptive
features as percentage of number of symptoms reported within the group
0 A1 A2 B1 B2 C1 C2 D1 D2
manual examination (n=30) (n=31) (n=32) (n=30) (n=32) (n=32) (n=32) (n=30) (n=30)
flexion P/L 0,913 0,752 0,712 0,737 0,811 0,784 0,729 0,806 0,741
extension P/L 0,924 0,839 0,858 0,796 0,887 0,901 0,822 0,874 0,845
Internal
(A) rotation P/L 0,903 0,875 0,901 0,843 0,811 0,863 0,879 0,901 0,895
hips external
asymmetry rotation P/L 0,911 0,854 0,829 0,889 0,903 0,909 0,807 0,882 0,831
(A) extension P/L 0,931 0,917 0,925 0,905 0,901 0,911 0,902 0,911 0,919
knees
asymmetry flexion P/L 0,942 0,909 0,924 0,913 0,933 0,939 0,928 0,906 0,936
dorsal flexion
(A) P/L 0,915 0,927 0,936 0,912 0,915 0,931 0,912 0,925 0,936
ankles plantar
asymmetry flexion P/L 0,923 0,931 0,928 0,94 0,922 0,917 0,934 0,919 0,93
L<P L<P L<P
L<P L<P L<P (10,7% (18,9% (14,7% L<P L<P
knee reflex L=P (23,5%) (17,5%) (13,4%) ) ) ) (10%) (13,3%)
(B) L<P L<P L<P L<P
reflexes achilles L<P L<P L<P (17,5% (13,2% (10,6% (21,4% L<P
asymmetry tendon reflex L=P (13,5%) (10,6%) (7,7%) ) ) ) ) (13,4%)
L>P L>P L>P L>P
L>P L>P L>P (84,4% (68,8% (65,7% (86,6% L>P
pain (L5) P/L 0 (87,5%) (87,5%) (83,3%) ) ) ) ) (83,3%)
L>P L>P L>P
L>P L>P L>P (93,8% L>P (84,4% (83,3% L>P
pain (L4) P/L 0 (93,4%) (79,2%) (86,6%) ) (91%) ) ) (86,6%)
L>P L>P L>P
L>P L>P L>P (90,7% (84,4% (78,3% L>P L>P
pain (L3) P/L 0 (92,7%) (75%) (90%) ) ) ) (70%) (76,6%)
L>P L>P L>P
touch (L5) L>P L>P L>P L>P (62,5% (81,3% (63,3% L>P
P/L 0 (87,5%) (87,5%) (70%) (75%) ) ) ) (80%)
L>P L>P
touch (L4) L>P L>P L>P (62,5% L>P (84,4% L>P L>P
P/L 0 (81,1%) (75%) (60%) ) (75%) ) (70%) (60%)
(B) L>P
touch touch (L3) L>P L>P L>P L>P (84,4% L>P L>P L>P
asymmetry P/L 0 (93,4%) (71,9%) (66,6%) (75%) ) (75%) (60%) (83,3%)
(C) 78,15
distinct stabbing 0 77,5% 71,2% 76,6% 78,15% 69,7% % 73,4% 70%
radicular stinging 0 16,1% 12,5% 13,3% 15,6% 21,9% 15,6% 20% 16,6%
pain (on
motion) indeterminate 0 6,4% 6,3% 10% 6,25% 9,4% 6,25% 6,6% 13,3%
(C) indeterminate 0 83,1% 84,4% 83,4% 81,2% 87,5% 78,2% 83,4% 86,6%
local pain
diffuse (on
stillness) stinging 0 12,9% 15,6% 16,6% 18,8% 12,5% 21,8% 16,6% 13,3%
For the purposes of the research, we selected 227 (117 women and 110 men) patients
with: (1) lower back pain (axial) (diagnosis based on neurologic examination), (2) L4L5 or
L5S1 space narrowing, without clear features of inter-vertebral disc rupture, but with an inter-
vertebral disc hypodensive area visible on a CT section (displayed using the authors software
(fig. 1) - parameters W(c) > 20%), (3) high concentration of immune complexes (CIC over
1,3ng/dl), (4) age 30-55 years.
Exclusion criteria: (1) a history of injury to the lower limbs or lumber part of the spine,
(2) a history of cancer, (3) past or ongoing collagenosis, (4) systemic neuromuscular diseases,
(5) past or ongoing viral hepatitis, (6) operated spine and/or lower limb joints. (7) bone
implants left after endoprosthetics. The patients were qualified to groups A1. D2 using the
authors software, the operation of which is based on the law of the stochastic fluctuation of
events, which at the same time ensures that the criteria for randomisation are met. The
condition of patients in the control group was examined once. Patients suffering from
neurovertebral conflict in the lumber area were assessed before therapy, on the day therapy
was completed and 30 days after the completion of therapy using: hip flexion asymmetry
(HFA), electricity skin threshold test (ESTT), visual analogue scale (VAS), circulating
immune complex concentration (CIC) assumed as an upper threshold standard indicator
(UTSI).
1. Group 0 (control group) consisted of 16 women and 14 men (aged 43,2 4,3)
healthy medical workers.
2. Group A(1) consisted of 16 women and 15 men (aged 45,3 6,4). in local treatment
we administered levamisole hydrochloride (1.2%) in usg gel by means of (EF)
3. Group A(2) consisted of 16 women and 16 men (aged 47,5 5,2). in local treatment
we administered levamisole hydrochloride (1.2%) in usg gel by means of (E)
4. Group B(1) consisted of 15 women and 15 men (aged 49.7 5.9). in local treatment
we administered 1.2% chloroquine diphosphate (arechin) in usg gel by means of (EF)
5. Group B(2) consisted of 17 women and 15 men (aged 51.6 7.2). in local treatment
we administered 1.2% chloroquine diphosphate (arechin) in usg gel by means of (E)
6. Group C(1) consisted of 16 women and 16 men (aged 50.8 7.1). in local treatment
we administered 'polfa's' borovinum by means of (EF)
7. Group C(2) consisted of 16 women and 16 men (aged 52.9 6.9). in local treatment
we administered 'polfa's' borovinum by means of (E)
8. Group D(1) consisted of 15 women and 15 men (aged 48.6 5.1). in local treating
we administered profenid (2.5% gel) by means of (EF)
Group D(2) consisted of 15 women and 15 men (aged 47.2 6.3). in local treating we
administered profenid (2.5% gel) by means of (E)
Application Method
The gel-like semi-liquid forms of levamisol, profenid, chloroquine and borovinum were
administered percutenously by means of: (1) traditional iontophoresis (E) and (2)
electrophonophoresis (EF) (a new standard in Polish physiotherapy). The system, developed
and implemented through the author's patent documentation, comprises a head (fig. 2a),
connected to the Sonoter power adapter (fig. 2b). It has the capability to administer drugs
percutaneously to a depth of 4-5 cm. 3 series of 5 treatments each were performed during the
course of the week from Monday to Friday (treatments lasting 15 minutes were administered
according to fig 3a and b below).
a b
Figure 2. (a) head for electrophonophoresis (EF), (b) power supply Sonoter for traditional
iontophoresis (E) and electrophonophoresis (EF).
The majority of drugs used in present day pharmacotherapy are substances administered
in an initially active form (i.e. they work immediately without any processing), such as e.g.
profenid or voltaren. Only a small group of drugs are administered as an inactive prodrug,
which acquire chemically active properties and take on the form of an actual drug with a
defined function, only after they pass through an extracellular section of the system such as
the intestines or plasma, or a cell's metabolic structure as is in the case of levamisol. The
initial activity of a drug is the condition which has to be fulfilled when attempting to
effectively use a drug by traditional means, such as iontophoresis or baroinjection. For this
reason, many drugs having interesting pharmacokinetic properties have been excluded from
local peracutenous treatment. According to laboratory findings, backed by clinical test results,
the new Polish method for percutaneous drug administration electronophonophoresis
enables some prodrugs to be activated outside the body, making them applicable for local use.
In a drug chamber head used in electrophonophoresis, which has been filled with a gel-
like solution containing a prodrug (levamisol), the effects of a specifically formed electric
field and mechanical vibrations overlap. One of the physical effects of this process is the
formation of cavitational microbubbles vibrating at a high frequency, whose alignment has
been determined by the electric field. Their internal temperature is several hundred degrees
Celsius whereas at the phase boundary the temperature reaches only a dozen or so degrees.
The inactive drugs enclosed within vibrating cavitational microvesicles are also subjected to
an electric field and as a result undergo many changes. Levamisol is metabolized in a number
of ways in the microsomal system of the liver, producing thus a range of products which
pharmacologically are very heterogenous. Laboratory tests, however, have shown that when
certain parametrical constellations are applied within the chamber head, a dominating
chemical conversion type, forming a defined kind of product with the desired
pharmacological properties, can be achieved [26]. It is worth noting that the mentioned
electric field accompanied by mechanical vibrations causes skin pores and ionic channels to
open to a greater degree, increasing the penetration of the drug into the cells from 15-20 mm
in the case of iontophoresis to 40-50 mm in the case of electrophonophoresis [18][19][26].
a b
Figure 3. RTG location head of electrophonophoresis: (a) RTG image showing location of
electrophonophoretis head; (b) body location scheme.
Measurement Methods
Pain is an individualized sensory perception, which appears as a psychological reaction to

pathological events happening in the body, which are registered by nervous system receptors.
Attempts at arriving at a quantative description of such a group of events mainly evolve
around estimate approximations based on subjective surveys, which are not entirely reliable
for interpersonal and intergroup evaluations.
One example of such an approach is the so-called Visual Analogue Scale, where in
response to a series of pre-defined diagnostic questions, through the use of a 10 cm ruler, the
patient is asked to define the pain intensity felt by him by pointing to a place on the scale (0
no pain at all, 10 - the most intensive pain imaginable).
In practice, however, patients find it difficult to reflect their personal perception of pain
using numbers, and since this method has been used as a means of simplifying the
measurement process, it leads to informational imbalance on an interpersonal and intergroup
comparative scale.
A reasonably balanced solution would be to focus attention on measurable physical
parameters of pain-related outcomes, in particular ones which are symmetry-oriented, which
would allow for an interpersonal and intergroup comparative analysis to be performed, and as
a result opening the doors to a wide array of statistical tests [23][70].
An example of this concept is the idea to present a quantative pain outcome scale as an
electrical current perception threshold in symmetrical points (left and right sided) of the skin
dermatomes of the limbs, anatomically linked to the location of the neuro-vertebral conflict,
and then to present the results using a ratio scale on a multi-axial coordinate system as so-
called asymmetry indicators, with a common point of reference (ESTT)(fig. 4-5).
Another measurement method used for determining the asymmetry scale as an outcome
of pain is the authors modification of Laseque's test based on an interactive, bioengineering
measurement of bend angles in the right and left hip joints (HFA- hip flection asymmetry),
the subsequent determination of the asymmetry indicator, which effectively eliminates the
inconsistencies of the first test resulting from muscle spasms (fig. 6).
In order to ensure alignment with the above, concentration changes of immune

complexes have been positioned on a ratio scale as an upper threshold standard indicator
(UTSI)(fig. 7), which reflects the quotient of the upper threshold standard value and the CIC
concentration value of the studied patient.
Questionnaire
A questionnaire on the symptomology of pain felt by the examined patients was

conducted using a Barbara Headley version of the VAS scale, which allowed for the
illustration of information on subjective pain features on a ratio scale. A questionnaire form
focused the patients attention on the most essential items of the questionnaire, towards which
the respondent specified his level of agreement by indicating a number on a scale from 1 to
10. The values of all 14 points of the score were added up and averaged for each patient and
subsequently for the examined group (I) before treatment, (II) on the day of the last treatment
session and (III) 30 days after the last treatment session [70]. VAS indicator:
score( x)
VAS =
score(max)
Electricity Skin Threshold Test (ESTT)
The electricity skin threshold test provides the chance to establish a non-specific but
strongly parameterized evaluation of the sensitivity of touch sensation receptors in and around
twin limb skin dermatomes bound anatomically with the source of pain (damaged
intervertebral disc). An interactive measurement of touch sensations induced by standardized
electric stimuli active around twin dermatomes of skin, which is innervated by touch
sensation receptors bound to the source of pain, provides the possibility to evaluate local
symmetries, which are quantatively related to the topography and intensity of the inter-
vertebral conflict in a given part of the spine [74].
The test standard involves placing 10 active electrodes (and one passive) on the patient as
shown in fig 5a, switching on the tester (fig. 4 a,b) sending electrical impulses with an
increasingly stronger amplitude beginning from electrode P1. The moment an electric current
sensation threshold appears, the patient presses on a signalling button, which results in the
system entering the threshold voltage value in the computer memory and activating the next
P2-10 electrodes. Once the test is complete, the system generates a summary diagram (fig.
5b), reflecting the local symmetries of electrical sensation in dermatomes bound to
subsequent inter-vertebral areas e.g. Th12/L1, L1/2, L2/3, L3/4, L4/5 and determining at the
same time the relationship of the left to the right side based on a formula (fig. 5c)
[22][28][101] .
a b
Figure 4. System for skin symmetry dermatomes diagnostics based on differences of electricity
perception (quantitative, symmetry indicator), for patients with low back pain syndromes (a) device for
performing an electricity skin threshold test, (b) location of electrodes - example.
a c
Figure 5. Electricity skin threshold test (ESTT): (a) scheme showing the location of electrodes
(electrode 1-10), (b) computer software with graph comparing the right and left leg sensitivity for
electricity potential; (c) asymmetry indicator ESTT: (V(R) - sensitivity threshold of electrode right leg
[V], V(L) - sensitivity threshold of electrode left leg [V].
Laseques Test
The equipment used to measure the bend angle in the hip joint in the straight leg raise test
is based on a standard couch assembly, in which a fragment of the bed has been cut out for an
adult leg length moveable part to form. The moveable section has been mounted to joints
placed placed at hip joint height, which allows for the limb to flex to a bend and straight leg
position. The drive comprises a microprocessor-driven electric servo mechanism, which

serves to change the beng angle of the tested limb (fig. 6a).
The measurement process starts from placing the patient on the couch and securing the
pelvis on the couch and the tested limb on the moveable part of the device. The control unit is
then reset and the measurement and patient number are entered. Once the measurement is
started, the servo mechanism changes the bend angle of the limb, stops when the patient
signalizes a pain sensation and measures the bend angle with an accuracy to 0,1 (fig. 6b).
c
a
Figure 6. Bioengineering prototype device for performing computer assisted Laseques test: (a)
prototype system; (b) concept of hip flexion asymmetry measurement based on Laseques test; (c)
mathematic formula (HFA).
The result of the modified straight leg raise test, demonstrated as a hip flexion asymmetry
(HFA) indicator, is calculated as ratio of the right hip joint flexion angle HF(R) and left hip
joint flexion angle HF(L) according to the above formula (fig. 6c) [22].
Measurement of Circulating Immune Complex

Concentration (UTSI)
The concentration of immunocomplexes was measured in samples collected from 30
healthy people from the control group (once) and from 233 patients from groups
A1,A2,B1,B2,C1,C2,D1,D2 on the day treatment was started and then after 30 days. CIC
tests were made by means of the ELISA test, in which the opacity of the serum reacting with
a specific antibody, bound to an indicator reagent is determined nephelometrically. The
reference parameters C(min)0,3 C(max)1,3 m/l (fig. 7a) of the test were used as a
reference point for calculating the (UTSI) upper threshold standard indicator. (fig. 7b) [22].
a
Figure 7. Conversion of stechiometrically determined CIC concentration parameters to a UTSI indicator
on a ratio scale: (a) a diagram showing the relation of example C1-n concentrations compared to the
upper standard threshold C(max); (b) conversion formula.
Statistic Tests
In the statistic research the following markers were applied:
a) T-Students test to grade importance level of differences among parameters (factors)

compared in specific patient groups, in specific time cycles.
b) Pearsons linear correlation quotient to grade interdependence of the results of
various measurement methods used amidst specific patient groups, in specific time
cycles.
Results
Table 2 shows the results of a Barbara Headley modified VAS test in patient groups A1,
A2, B1, B2, C1, C2, D1, D2 with diagnosed neurovertebral conflict in the L4/5 or L5/S1
areas. The results were obtained (I) before treatment, (II) on the last day of treatment and (III)
30 days after treatment was finished. It can be clearly seen that the pain intensity before
treatment (I) is comparable to that of all the tested groups. The results after the completion of
treatment (II) show clear differentiation, i.e. the most significant painkilling effect in groups
A1,A2 i D1,D2, a slightly smaller one in groups B1, B2 and a moderate one in groups C1,
C2. After 30 days from commencing treatment the painkilling effect disappears in group D1,
D2, but remains in groups A1,A2 i B1,B2, and persists in groups C1, C2 as well, however,
not to an equal extent. These results are statistically significant (table 3). The treatment results
employing the electrophonophoretic (EF) and ionophoretic (E) methods in groups
A1,B1,C1,D1 demonstrate highest correlation in groups D1, D2, weaker in groups C1,C2 i
B1,B2, and the weakest in groups A1, A2 (table 4).
Table 2. Barbara Headley modified Visual analog scale (VAS) test result in patient
groups A, A1,B, B1, C, C1, D, D1 diagnosed with neurovertebral conflict in the L4/5 or
L5/S1 regions
Measurement
GROUP I (before treatment) II (1 day after treatment) III (1 month after treatment)
A1 0,621 0,117 0,285 0,072 0,311 0,065
A2 0,549 0,108 0,453 0,058 0,534 0,042
B1 0,644 0,097 0,312 0,049 0,465 0,037
B2 0,609 0,103 0,495 0,037 0,492 0,049
C1 0,598 0,084 0,473 0,041 0,521 0,054
C2 0,619 0,091 0,492 0,063 0,534 0,072
D1 0,573 0,075 0,271 0,081 0,562 0,061
D2 0,592 0,111 0,489 0,095 0,611 0,059
Table 3. Evaluation of the level of significance of differences in groups

A1,A2,B1,B2,C1,C2,D1, D2 for the VAS test results obtained before treatment (I),
shortly after treatment (II) and 30 days after completing treatment (III)
Significance of differences
A1(I) A1(II) A1(I) A1(III) A1(II) A1(III)
p < 0,05 p < 0,05 p < 0,1
P < 0,1 P < 0,5 P < 0,5
B1(I) B1(II) B1(I) B1(III) B1(II) B1(III)
p < 0,05 p < 0,1 p < 0,5
P < 0,1 P < 0,5 P < 0,5
C1(I) C1(II) C1(I) C1(III) C1(II) C1(III)
p < 0,1 p < 0,5 p < 0,5
P < 0,5 P < 0,5 P < 0,5
D1(I) D1(II) D1(I) D1(III) D1(II) D1(III)
p < 0,05 p < 0,5 p < 0,05
P < 0,1 P < 0,5 P < 0,1
Figure 8. Evaluation of the VAS test results obtained (I) before treatment, (II) shortly after treatment
and (III) 30 days after completing treatment.
Tab. 4. Linear correlation (Pearsons indicator) between hip flexion asymmetry (HFA),
electricity skin threshold test (ESTT), upper threshold standard indicator (UTSI) and
VAS parameters, measurement in the groups: A1,A2,B1,B2,C1,C2,D1,D2
Indicator correlations
VAS /HFA VAS /ESTT VAS /UTSI
Measurement Measurement Measurement
Group I II III I II III I II III
A1 0,512 -0,525 -0,509 0,536 -0,535 -0,505 0,421 0,467 0,441
A2 0,535 -0,422 -0,381 0,506 -0,407 -0,393 0,435 0,321 0,309
B1 0,498 -0,519 -0,477 0,521 -0,545 -0,512 0,397 0,435 0,415
B2 0,479 -0,417 -0,367 0,531 -0,401 -0,374 0,413 0,419 0,391
C1 0,507 -0,489 -0,424 0,496 -0,432 -0,401 0,407 0,425 0,416
C2 0,483 -0,401 -0,331 0,487 -0,403 -0,365 0,381 0,409 0,401
D1 0,524 -0,542 -0,511 0,512 -0,557 -0,461 0,431 0,427 0,431
D2 0,488 -0,412 -0,393 0,529 -0,471 -0,411 0,388 0,416 0,372
The electrophonophoresis treatment (EF) results (VAS) are statistically significant (table
2-3) and correlate with the results obtained using the iontophonoretic (E) method in groups
A1, B1, C1 and D1. Correlation is greatest in groups D1 and D2, weaker in groups C1, C2
and B1,B2 and weakest in groups A1 and A2 (table 4).
Table 5. Hip flexion asymmetry (HFA) in patient groups 0, A1, A2, B1, B2, C1, C2, D1,
D2 with lower back pain ( L4/5 or L5/S1)
Measurement
0 0,942 0,027
A1 0,622 0,078 0,923 0,048 0,841 0,051
A2 0,635 0,065 0,761 0,061 0,685 0,072
B1 0,656 0,043 0,904 0,052 0,815 0,069
B2 0,624 0,067 0,854 0,059 0,783 0,074
C1 0,594 0,049 0,803 0,063 0,781 0,081
C2 0,615 0,061 0,744 0,056 0,715 0,078
D1 0,611 0,053 0,935 0,044 0,675 0,082
D2 0,623 0,072 0,745 0,057 0,651 0,089
Table 5, fig. 9 shows the results of the HFA, tab. 7, fig.10 shows the result of the ESTT
tests in control group (0) and in patient groups A1, A2, B1, B2, C1, C2, D1, D2 diagnosed
with neurovertebral conflict in the L4/5 or L5/S1 areas. The results were obtained (I) before
treatment, (II) on the last day of treatment and (III) 30 days after treatment was finished. It
can be clearly seen that the pain intensity before treatment (I) is comparable to that of all the
tested groups A1, A2, B1, B2, C1, C2, D1, D2 and is distinctly different from control group
0. The results for tests HFA (tab. 5, fig. 9) and ESTT (tab. 7, fig. 10) after the completion of
treatment (II) show clear differentiation, i.e. most evident symmetry recovery in groups A and
D, a slightly smaller recovery in group B and a moderate one in group C. After 30 days from
commencing treatment the effect disappears in group D but remains in groups A and B, and
persists in group C as well, however, not to an equal extent.
Table 6. Evaluation of the significance of the difference between the hip flection
asymmetry(HFA) Test in the control group (0), and the results eight patient groups A1,
A2, B1, B2, C1, C2, D1, D2 obtained before treatment (I), shortly after treatment (II)
and 30 d ays after treatment (III)
group I II III
0 A1(I) 0 A1(II) 0 A1(III)
0 A1 p < 0,01 p < 0,5 p < 0,5
0 A2(I) 0 A2(II) 0 A2(III)
0 - A2 p < 0,01 p < 0,05 p < 0,01
0 B1(I) 0 B1(II) 0 B1(III)
0 - B1 p < 0,01 p < 0,5 p < 0,1
0 B2(I) 0 B2(II) 0 B2(III)
0 - B2 p < 0,01 p < 0,1 p < 0,05
0 C1(I) 0 C1(II) 0 C1(III)
0 - C1 p < 0,01 p < 0,1 p < 0,05
0 C2(I) 0 C2(II) 0 C2(III)
0 - C2 p < 0,01 p < 0,1 p < 0,05
0 D1(I) 0 D1(II) 0 D1(III)
0 - D1 p < 0,01 p < 0,5 p < 0,01
0 D2(I) 0 D2(II) 0 D2(III)
0 - D2 p < 0,01 p < 0,1 p < 0,01
Figure 9. Distribution of the hip flection asymmetry (HFA) test.

Table 7. Electricity skin threshold test (ESTT) in the control group (0) and patient
groups A1, A2, B1, B2, C1, C2, D1, D2 with lower back pain ( L4/5 or L5/S1)
Measurement
0 0,931 0,037
A1 0,582 0,078 0,924 0,061 0,872 0,068
A2 0,598 0,069 0,742 0,064 0,655 0,072
B1 0,601 0,063 0,876 0,054 0,835 0,057
B2 0,614 0,075 0,821 0,063 0,794 0,07
C1 0,611 0,071 0,808 0,069 0,758 0,079
C2 0,597 0,081 0,738 0,077 0,721 0,086
D1 0,598 0,075 0,936 0,068 0,654 0,081
D2 0,603 0,072 0,711 0,078 0,632 0,093
Table 8. Evaluation of the significance of the difference between the electricity skin
threshold test (ESTT) in the control group (0), and the results for patients in groups A1,
A2, B1, B2, C1, C2, D1, D2 obtained before treatment (I), shortly after treatment (II)
and 30 days after treatment (III)
group I II III
0 A1(I) 0 A1(II) 0 A1(III)
0 A1 p < 0,01 p < 0,5 p < 0,5
0 A2(I) 0 A2(II) 0 A2(III)
0 - A2 p < 0,01 p < 0,05 p < 0,1
0 B1(I) 0 B1(II) 0 B1(III)
0 - B1 p < 0,01 p < 0,5 p < 0,1
0 B2(I) 0 B2(II) 0 B2(III)
0 - B2 p < 0,01 p < 0,1 p < 0,05
0 C1(I) 0 C1(II) 0 C1(III)
0 - C1 p < 0,01 p < 0,1 p < 0,05
0 C2(I) 0 C2(II) 0 C2(III)
0 - C2 p < 0,01 p < 0,1 p < 0,05
0 D1(I) 0 D1(II) 0 D1(III)
0 - D1 p < 0,01 p < 0,5 p < 0,01
0 D2(I) 0 D2(II) 0 D2(III)
0 - D(2) p < 0,01 p < 0,1 p < 0,01
Table 9. Upper threshold standard indicator (UTSI) of circulation immunocomplexes

(CIC) in control group (0) and patient groups A1, A2, B1, B2, C1, C2, D1, D2 with lower
back pain ( L4/5 or L5/S1)
Measurement
0 0,545 0,061
A1 2,25 0,215 1,12 0,137 1,36 0,112
A2 2,18 0,221 1,78 0,145 2,21 0,245
B1 2,13 0,178 1,58 0,157 1,88 0,138
B2 2,28 0,237 1,85 0,179 1,92 0,261
C1 1,99 0,209 1,68 0,203 1,77 0,153
C2 2,09 0,197 1,89 0,161 1,94 0,214
D1 2,14 0,237 2,05 0,193 2,21 0,236
D2 2,23 0,182 2,18 0,189 2,15 0,197
Figure 10. Distribution of electricity skin threshold test (ESTT).
Table 10. Evaluation of the significance of the difference between the upper threshold
standard indicators (UTSI) in the control group (0), and result for patients in groups
A1, A2, B1, B2, C1, C2, D1, D2 obtained before treatment (I), shortly after treatment
(II) and 30
days after treatment (III)

group I II III
A1 p < 0,01 p < 0,01 p < 0,1
A2 p < 0,1 p < 0,5 p < 0,5
B1 p < 0,05 p < 0,05 p < 0,1
B2 p < 0,1 p < 0,1 p < 0,5
C1 p < 0,1 p < 0,5 p < 0,5
C2 p < 0,5 p < 0,5 p < 0,5
D1 p < 0,5 p < 0,5 p < 0,5
D2 p < 0,5 p < 0,5 p < 0,5
UTSI test results after treatment completion (II) using electrophonophoresis (EF) also
show major differentiation, i.e. there is a decrease of the CIC concentration to the upper
standard threshold level C(max) in the group A1, slightly smaller decrease in group B1 and a
moderate one in group C1. Group D, however, showed a high, initial (I) CIC concentration.
The results are statistically significant (tab. 10). After treatment (II) using iontophoresis ( E),
groups A1, B1 and C1 showed a significance threshold level fall in CIC concentration (table
10, fig.11).
Figure 11. Changes in the distribution level of immune complexes (CIC) based on upper threshold
standard indicator (UTSI).
30 days after the completion of treatment (III) in groups A, B and C, low CIC
concentrations persist near measurement (II) level, however, they have an increased value in
group D, nearing the initial (I) values. The results are statistically significant.
Table 11. Linear correlation (Pearsons indicator) between hip flexion asymmetry
(HFA), electricity skin threshold test (ESTT) and upper threshold standard indicator
(UTSI) measurement in the groups: A1,A2,B1,B2,C1,C2,D1,D2
Indicator correlations
HFA/ESTT HFA/UTSI ESTT/UTSI
Measurement Measurement Measurement
Group I II III I II III I II III
A1 0,903 0,913 0,909 0,785 -0,875 -0,821 0,811 -0,849 -0,817
A2 0,909 0,887 0,895 0,741 -0,183 -0,167 0,795 -0,211 -0,195
B1 0,897 0,903 0,903 0,723 -0,631 -0,607 0,784 -0,667 -0,632
B2 0,877 0,891 0,888 0,696 -0,339 -0,283 0,749 -0,387 -0,351
C1 0,873 0,894 0,891 0,714 -0,247 -0,214 0,756 -0,269 -0,245
C2 0,858 0,904 0,909 0,735 -0,206 -0,172 0,737 -0,221 -0,196
D1 0,891 0,912 0,887 0,709 -0,093 -0,035 0,806 -0,097 -0,041
D2 0,865 0,871 0,851 0,701 -0,011 -0,009 0,797 -0,016 -0,007
Conclusions
Disc disease with neuro-vertebral conflict, which can lead to hernia, is usually a
multietiological process. Immunological phenomena (which cause a gradual degradation of
the colloid's structure) can greatly contribute to such an outcome. Electrophonophoresis has
proven method capable of sending medicine to an aggravated location within an intervertebral
disc:
1. The average values of the UTSI indicator, defining the CIC immune complex
concentration in groups A1, A2, B1, B2, C1, C2, D1, D2 comprising patients
diagnosed with an intervertabral disk cyst in the L4/5 or L5/S1 region, having a
cross-section surface area >20%, have been shown to be significantly increased
compared to patients from the control group (0).
2. The HFA and ESTT indicator values in groups A1,A2,B1,B2,C1,C2,D1,D2,
comprising patients diagnosed with an intervertabral disk cyst in the L4/5 or L5/S1
region, have been shown to have increased asymmetry compared to patients from the
control group (0).
3. Using electrophonophoresis (EF) for percutaneous treatment leads to a decrease in
pain related discomfort on a VAS scale and to an increase in the HFA and ESTT
parameter symmetry more clearly and in a more statistically significant way than
after using iontophoresis (E).
4. Percutaneous treatment, mainly in the case of electrophonophoresis (EF) led to a
decrease of pain-induced discomfort on the VAS scale and to an increase of HFA and
ESTT parameter symmetry, especially after the administration of levamisol and
chloroquine, influencing most probably the decrease of cystic immunological
activity, the specific marker of which may be the normalization in the UTSI
circulating immune complex concentration. This phenomenon, despite being
methodologically non-specific, is to a high extent statistically significant and does
not occur during short-term pain regression following the administration of Profenid.
Discussion
Based on literature reports, it can be accepted, that neuro-vertebral disease, which
subsequently evolves into neuro-vertebral conflict, has to be treated as a multiethiological
process, which leads to a progression of activity and structural destruction of the colloid
(where immunological processes play one of the main roles)[2][3][5][7][8].
Hernia is the anatomical displacement of the contents of the intervertebral disc beyond
the damaged intervertebral fibrocartilage and leads to pressure being exerted on the
neighbouring tissues[50]. It may be caused by an injury, chronic degenerative overload-
induced changes, metabolic changes or immunological and inflammatory changes to the
colloid[7][8]. This causes the subsequent layers of the intervertebral cartilage to crack and
increases pressure on the ligamentum longitudinale posterius. Depending on the dominating
shift vector of the injury's energy, central or lateral hernia is formed[10][32][33][35]. The
course of this process, stimulated by an unfavourable motion pattern, leads to a chronic
movement of the hernial sac, often without the development of a vascular cluster. Such cases
are effectively addressed without any side effects through traditional surgery[42].
Prolonged pressure of the hernia on the long and short posterior ligament, with a
vascularized sac, can however lead to contact between the nucleus pulposus and the
circulatory system and as a result intensify the repair process by expanding the vascularized
area. The action of a stimulus exceeding to a significant extent the durability of the tissue,
leads to severe hernia, whose contact with the immune system becomes increasingly more
pronounced[40][47][81].
The onset of intervertebral disc disease may have various causes and may be caused by:
(1) chronically progressing backbone geometry change, leading to disc overload, damage to
proteoglycanes and weaker disc flexibility, (2) acute overload of a healthy backbone, leading
to microcracks in the disc, cartilage and bone, leading to revascularization and a series of
repair processes, (3), acute hernia, leading to sudden changes in the structure and parameters
of the colloid, (4) rapid degradation of the biochemical composition of the colloid, resulting
from enzymatic defects, (5) rapid degradation of the colloid, e.g. due to a history of infection,
which led to local destruction of the bone and disc structure and the development of a fluid
cavity separated by a fibrous cartiladge wall [51][52][56][57][58].
As vessels come into contact with the colloid, it becomes susceptible to infection when
operated, following spinal injections [57], microsurgical interventions [46] and laminectomy
[55]. Pus development in the colloid may subside, undergo sequestration and finally end up
leaving a single cyst encapsulated in a calcic body or become disseminated [4][5][6][10].
Inflammation with pus present may initiate an additional asceptic autoimmunological chain of
events, which manifest themself through immunoglobulin, lymphocyte and macrophage
deposits in the tissue, and accelerates the functional and structural destruction of the colloid
[29][30][31]. The process may occur as local inflammation of the archanoid or dura mater of
the spinal cord, causing changes in the flexibility of the colloid, proteolythic enzyme activity,
immunoglobulin levels, which radiologically may manifest themselves as a vacuum
phenomenon [37][43][47][48][49].
The liquid contents of cysts, which on one hand do not come into much contact with the
vascular system, but on the other do so with the structure of the disk, become an area of
antigenic stimulation, and in the case of a general infection, a convenient place for the
development of an invasive strain [44]. The intensification of immunological processes in a
space encapsulated within a cohesive tissue, leads to their rapid dissemination within the
follicular and web-like structure of the colloid, causing an enzymatic degradation of the
structure, reduction of the colloid's pressure and aggravation of the neuro-vertebral conflict
[52][53].
Developing vascular clusters direct the migration of lymphocytes, macrophages, and
blastocells for fibroblasts in the developing cyst... Vascular contact with the tissue, which had
remained practically isolated, results in renewed verification of its HLA-DR membrane
antigens. This in turn leads to relentless rest pain, often ensuing at night, which intensifies
along the cervical route pathway when performing movements, and which does not respond
well to analgesic treatment [60][61]. This pain feature and the toxic consequences of using
large doses of analgetics are good reason for using percutaneous treatment by means of
electrophonophoresis (EF).
A frequently encountered event in CT and MR screening , and even in overview x-ray
imagery are cysts, which are visible in intervertebral space sections or in vertebral body
sections, which are rarely related to the pain syndrome being analyzed [22][60].
It is thus worth remembering, that relentless rest pain occurring in a neurovertebral
conflict and weak response to standard pain relief medicine, reported not only by the patients
involved in the above tests, may be the first sign of contact between a damaged intervertebral
disc and the immune system. Further development of a clinical situation depends on the
positive or negative verification of the colloid. Positive verification causes deterioration of the
regeneration process and suppression of inflammatory reactions, however, a non-self
verification initiates a whole array of immunological responses, aimed at destroying the body
which has been identified as foreign. This inference is confirmed by numerous scientific
findings on changes in a damaged intervertebral disc, namely concerning: (1) enzymatic
activity, (2) immunological activity, (3) metabolic activity, (3) pressure parameters and
oxygen concentration [64][65][66][67][68].
In this context, the short-term effect of the analgetic action of profenid and paradoxically
the significant and long-term analgetic effect of levamisol and chloroquine takes on an
entirely different meaning [69]. The first does not cause a decrease of CICs and the latter do
so to a considerable extent. The above observation may be non-specific proof of suppression
of an inflammatory reaction in a damaged disc as a result of the administration of medicine
such as chloroquine, levamisol and even use of borovinum, which have a proven
immunomodulatory effect.
As referenced by many sources, vascular clusters entering the disc as well as the
proliferation of granulation tissue intensifies the local production of chemical pain mediators
and enzymes leading to a protheolythic breakdown of the network-like and micellar structure
of the colloid and a decrease of the discs flexibility [72][73].
A similar mechanism can sometimes be seen following laminectomies of the
intervertebral disc, where despite partial success manifested by cervical pathway pain
centralisation or remission, contact between the remaining fragments of the discs tissue and
the circulatory and immune system is initiated or intensified [2][13][29][30][36].
This fact also explains the causes of local pain persisting for many months and even years
after operation. Literature frequently confirms, that in this type of pain the concentration of
immune complexes and immunologlobulins in the blood is higher, which is proof of an
immunological reaction appearing alongside the pain [54][61].
This fact has been the reason why the author has decided to use CICs as a non-specific
marker in his research.
Coming back to hernias, inflammation progressing around an imbedding vascular cluster
may be one of the reasons for the onset and growth of a vertebral body cyst [34]. It may also
be a pain relapse stimulator and a cause for accelerated colloid structure destruction [102]. A
long-term immunological reaction within a colloid leads to chemotaxis of neutrophil
granulocytes, and after their breakdown to the release of large amounts of proteolytic
enzymes, which gradually disintegrate the primary, secondary and tertiary structure of the
colloid, causing a phased out decrease of the inter-vetebral body dimension [79][80].
Maintenance of the flexibility of an intervertebral disc is the basic, macroscopic parameter in
the functioning of the colloid, which determines the support triads function accuracy. The
parameter correlates in various degrees with provocation, the vacuum symptom, as well as the
physical, biochemical and immunological parameters of the colloid.
Based on the above literature findings and self-performed research, the author suggests
that the criterion for selecting patients to particular therapy groups (where an immunological
factor is present) be the W( c ) indicator, drawing attention to the fact, that once its value is
exceeded by 20-25%, the probability of finding an increased concentration of CICs exceeds
65-70% [22].
It needs to be said that the multiethiological hypothesis, especially the immunological

ethipathogenesis of a neurovertebral conflict has been the subject of numerous verifications,
during which imaging examination results were correlated with anatomopathological tests on
post-operational and sectional material, obtaining thus many resultant criteria [87].
Long before the introduction of tomographic techniques, attention had been drawn to the
vacuum symptom appearing occasionally in X-ray images, which indicated the presence of
a cyst in the vertebral body communicating with the colloid and sometimes undergoing
calcification. With time, these cysts began to be considered as a factor causing backbone
dysfunction and contributing to the development of hernia.
The introduction of tomographic techniques and fiberoscopy has led to the development
of a greater number of radiological and biochemical criteria regarding a disc's involution.
Various features of a persons genes, lifestyle, nutrition as well as psychological construction
have been proven to be an influence [75][76][82][83][85][86][87].
According to many authors, hypodensive areas, where the intervertebral disc comes into
contact with the vertebral body, are predisposed to the development of hernia. Collections of
criteria concerning changes in the intervertebral disc in the course of systemic diseases have
been prepared and they are often present with an increased immunological reaction marker
level.
Attention has also been drawn to the characteristic involutional alterations in the disc,
which appear in the images of people, who do not experience pain. CT and MRI image
correlation with histological and contrast examinations using X-ray absorbers as well as spin
and fluorochrome labels has led to better detection of even the smallest cysts, which may
initiate intervertebral disc disease.
The development of percutaneous diagnostic methods and intervertebral disc treatment
techniques (LASE, IDET, discography, chemonucleolysis) using catheters has led to a
considerable improvement of the diagnostic and treatment quality, causing in only a small
number of cases infectious post-operative complications, less frequent than after
laminectomy. Direct examinations on colloid samples enabled the evaluation of: (1) the
physical and chemical properties in different stages in the degeneration process of a disc; (2)
changes in the physical and chemical properties coexisting with postural defects; (3) changes
in the proteolythic enzyme activity; (4) changes in the metabolic pathway; (5) changes in the
structure of proteoglycans and collagen; (6) lymphocyte and macrophage content in fresh
pouches and hypodensive areas; (7) immunoglobulin residue in the colloid; (8) colloid
calcification; (9) correlation in the activity between the local (within the colloid) and
peripheral immunological processes; (10) correlation between the morphological features of
cysts in a CT or MRI image and immunological process activity [89][90][91][92].
Summarizing the above literature findings, consideration should be given to the concept
of a cyst located around the support triad with high probability of it being a symptom of an
ensuing cascade of immunological processes affecting the intervertebral disc. The processes
lead to mechanical disorders in the support triads function through changes in the colloid's
metabolic function, structure, electric charge and hygroscopicity. This may lead to a
considerable change in the approach to treating certain types of backbone pain disorders. The
concept focuses on finding a little invasive way for determining the onset of an inflammatory
process affecting the intervertebral disc and using more specific treatment, which would stop
or decelerate the destruction of the colloid. Gaining control over the early stages of a disease
affecting a disc may extend the longevity of the affected body part, decrease the number of
laminectomies and costly laparoscopic operations such as IDET, LASE, ALIF, and
PLIF[94][95][96][97].
Traditional surgical methods, by initiating contact between the colloid and the vessel
system, can cause an immunological and proliferative reaction. Postoperative administration
of local proliferation modulators decreases pain. Surgical application of local modulators of
proliferation decreases pain immediately and for the long-term
[12][24][25][77][88][99][100].
The aim of this work was to try to determine whether the implementation of the Polish
method of electrophonophoresis, where a drug with confirmed localized immunomodulatory
and analgesic characteristics is infused into the body, will result in a longer lasting clinical
effect than after using NSAIDS.
In previous research we proved that percutaneously administered levamisol
[22][59][78][93] led to a longer remission of pain (compared to phenylobutason), both of a
nervous and located background. What's more, it decreases the level of immune complexes
(CICs). The main aim of this research was to arrive at an answer to the question if similar
clinical results can be achieved by using chloroquine and borovinum.
In the group of patients which was treated locally by means of profenid, after 15 attempts
it was possible to see an almost full symmetrical recovery in laseque's (HFA),
electrosensorical (ESTT) and visual analogue VAS test. However, profenid does not have a
significant impact on CIC levels. The ailments relapsed mostly after 1,5 months time. This
shows that profenid affects pain-feeling mediators and non-specific inflammable reactions
(around the root), but has no influence on characteristic immunological reactions, in spite of
the fact that the administered medicine reached the cyst. In the patient groups treated by
means of levamisol, pain (both root and located) subsided quickly.
The survey (VAS), Laseques (HFA) and electrosensorical tests proved that a slightly
weaker effect appeared after chloroquine, and a far weaker one after borovinum. Pain
syndromes of the spine caused by a cyst in the intervertebral disc are more severe and chronic
compared to neurovertebral syndrome induced by mechanical, moderate pressure made by a
hernial sac, due to a local immune response. Long-term pain-killing effects achieved after
administering chroquine and levamisol may be explained as having been caused by the local
inhibition of an immune response. The applied method most probably enables molecules of
all administered drugs to reach the root as well as the cyst.
A fall in immune complexes was reached as early as after 15 levamisol infusions. The
clinical effects described above correlate well with a sensitive, yet unspecific immunological
parameter circulating immune complex concentration (CIC), which shows near-normal
values (including long-term pain remission) especially after the administration of levamisol.
A weaker response is caused by chloroqine, while borovinum produced unspecific effects.
This can be considered a significant factor confirming the percutaneous, modulating influence
of chloroquine, borovinum and levamisol on the local source of immune inflammatory
responses and the related level of immune complexes (CIC) circulating in the blood[78].
Thanks to electrophonophoresis, it became possible to achieve highly concentrated drugs
modifying the course of inflammatory reactions (e.g. cysts). For this reason even small doses
(6-8mg) of chloroquine or levamisol concentrate to a greater extent in the focus area than
after oral administration of the standard dose (Levamisol 150), (Arechin 250mg). Our method
has yet another advantage: it does not harm other vessels.
The use of a common ratio scale both for the evaluation of subjective pain features
(VAS), changes in CIC concentration (UTSI) and most importantly for the evaluation of
sensation (ESTT) and biomechanical (HFA) consequences of pain, well reflects the
interrelationships between the regulatory processes affected by the medical condition and
facilitates the use of statistical methods in differential diagnostics and monitoring of the
patient.
The main objective of this research, however, was to focus the attention of doctors on the
possibility of there being an immunological etiology in many recurring neurovertabral
conflicts, which often, despite costly treatment, leads to a deterioration of a patient's quality
of life, or even to permanent disability.
I hope that this clearly defined intention, supported by initial clinical research, will
encourage many practitioners to perform individual tests, and in justified cases also to revise
the concept of the illness and treatment methods, as well as to make attempts at percutaneous
therapy using immunomodulatory medicine.
I would very much like for the presented results to serve as encouragement to performing
more widely-spread research on the use of percutaneous local therapy, which would facilitate
the development of the most optimal treatment standards and become an element of causative
treatment for difficult and onerous medical conditions, which often times lead to permanent
disability.
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Chapter III
Myofascial Pain Syndrome in the Pelvic

Floor: Etiology, Mechanisms,
Symptoms, Diagnosis, and Treatment
F. Itza Santos,*1 D. Zarza,2 L. Serra Llosa,3 F. Gmez Sancha,4

J. Salinas,5 and E. Bautrant 6
1
Pain expert. Hospital Clnico San Carlos. Madrid. Spain
2
Neurophysiologist. Hospital de Mostoles. Madrid. Spain
3
Physiotherapist. Hospital Clnico San Carlos. Madrid. Spain
4
Urologist. Clnica Cemtro. Madrid. Spain
5
Urologist. Hospital Clnico San Carlos. Madrid. Spain
6
Gynecologist. Centre mdical lAvance. Aix en Provence. France
Abstract
Myofascial pain syndrome in the pelvic floor is a common condition, originally
described by Drs Janet Travell and David Simons, involving the musculoskeletal system;
there is a high percentage of misdiagnosis and a high failure rate of medical interventions
and, therefore, of frustrated specialists and patients. The etiology includes urologic,
gynecologic, gastrointestinal, proctologic, neurological, and musculoskeletal problems.
Muscle injury can occur when soft tissues are exposed to single or persistent episodes of
muscular overload. Myofascial pain syndromes are characterized by the development of
myofascial trigger points that are locally painful when stimulated. These trigger points
are hyperirritable spots within a taut band of hypercontracted extrafusal muscle fibers.
The trigger point and the taut band can be palpated, which provokes the typical referred
pain. Affected muscles are usually shortened and have an increased tone and tension.
Diagnosis is done based on the history, physical examination, and neurophysiologic tests.
Treatment requires medical, psychological, and physical therapies, including local
* Correspondence: Dr. Itza, fitza@arrakis.es.

78 F. Itza Santos, D. Zarza, L. Serra Llosa et al.
infiltrations with lidocaine, dry needling, botulinum toxin injections, and several
physiotherapeutic and psychological techniques.
Keywords: Pelvic Floor, Trigger Points (TrPs), Myofascial Pain, Referred Pain, Infiltrations,
Physiotherapy.
"The only true wisdom is knowing you know nothing"

Socrates
1. Introduction
Myofascial syndrome in general, and in the pelvic floor in particular, is a well-
differentiated entity thanks to the studies of Janet Travell and David G. Simons, published
since 1983. With the passage of time, the concept of myofascial pain has been approached in
different ways. In 1952 Dr. Travell published the first compendium of individual pain
patterns that are characteristic of each of the muscles that most often develop this discomfort
throughout the body [3, 22].
Later she herself recognized the multiplicity of factors that perpetuate the trigger points
of this pain, which transform a simple muscle pain syndrome into a chronic, complex, and
debilitating pain.
It is the most common cause of musculoskeletal pain, yet its diagnosis is often
overlooked. Treatment is poor or ineffective, probably due to insufficient training of
professionals in this pathology.
Moreover, chronic prostatitis, a condition that caused and keeps on causing concern for
professionals and patients alike, seems to be closely related to myofascial pain and
dysfunction. This was how Zermann et al. understood it in 1999 in their article "Chronic
Prostatitis: A Myofascial Pain Syndrome?" This study involved 103 men, and 92.2% of those
who had chronic pelvic pain/chronic prostatitis presented with pelvic floor dysfunction and
negative microbiological tests, and a significant number had neurological dysfunction [18].
Similarly, in the same period Anderson et al. presented a paper recommending
physiotherapy treatment for myofascial release of type III chronic prostatitis. They concluded
that this treatment might be effective and lasting [19].
Earlier, in 1977, Sinaki et al. of the Mayo Clinic had published an interesting study on
pelvic floor tension myalgia in 94 patients, in which a combined treatment of diathermy,
Thiele massage, and relaxation exercises gave good results [20].
Other authors have defined this type of symptomatology as the short pelvic floor
syndrome, due to loss of muscle length and the consequent functional problems [35,36].
As we shall see, we will come across a number of terms that we are very familiar with
and that are interrelated: myofascial pain, muscle hypertonicity, trigger points, chronic
prostatitis, physiotherapy, referred pain, sensitization of the nervous system, etc. In all these,
the muscle and the nervous system form the central axis.
We will also encounter a number of disease entities which, although very different in
origin, have a common aspect: the myofascial pain syndrome. Thus, it can be deduced that
treatment will be very similar in all these cases. Among these entities are chronic bacterial
Myofascial Pain Syndrome in the Pelvic Floor 79
prostatitis [30,31], chronic nonbacterial prostatitis/chronic pelvic pain syndrome

[30,31,100,101], interstitial cystitis [30,32,35,36,49,50,70, 99,100], levator ani syndrome
[26,34,70], urgency-frequency syndrome [35,36, 49], prostatodynia [32,35,36], endometriosis
[33,50,70], pyramidal syndrome [35,36], vulvodynia [35,36,49,70,92], coccydynia [35,36],
irritable bowel syndrome [70,98], and abdominal scar pain [53].
M scu lo n or m a l
M scu lo ac or ta d o c on b a n d as d olorosa s
Figure 1. Normal Muscle Contracted muscle with tender bands.
Today we know that the myofascial syndrome is a regional pain disorder that affects the
muscles and fascia, in such a way that the muscles involved have a trigger point (TrP) or
trigger points as associated components.
The muscles involved have the following characteristics [21, 22]:
Pain produced and maintained by one or more active TrPs.

The TrP is located within a taut band of the muscle or its fascia.
The taut band and the TrP can be palpated, which provokes referred pain.
The ability of the affected muscle to stretch is restricted, and often the muscle cannot
stretch completely. The muscle is contracted (Figure 1).
The pattern of referred pain is specific for each muscle.
The muscles adjoining the affected muscles are also tense on palpation.
There is a spasm response to firm pressure on an active TrP, because of a transient
contraction of the muscle fibers in the taut band. This is called the local twitch
response.
Moderate but sustained palpation of a TrP tends to accentuate the pain.
The maximum force of contraction of the affected muscle is decreased, with muscle
weakness and increased fatigability, but without atrophy or muscle fibrosis.
The TrPs are activated by direct trauma, pressure, and/or muscle overload.
Autonomic regional and segmental changes coexist with the above symptoms: local
changes in the skin, increased sweating, changes in local temperature, and sometimes
small local edemas.
In some cases suprapubic edema, sacral edema, or edema in the vaginal fornices is
especially important. In rare cases, the swelling is so pronounced that it can lead to
misdiagnosis and to the belief that it is the only cause of the problem.
Sometimes there is no myofascial trigger point, but what is known as a Tender Point;
in such a point there is no local twitch response nor a taut band, and the pain is
localized and intense.
2. Brief Overview of the Anatomy

of Pelvic Floor Muscles
The pelvic floor or perineum is that part of the trunk that is located below the pelvic
diaphragm. It is located in the inferior outlet of the pelvis [3, 4, 5].
The word perineum is derived from the Greek word perineos, which means the space
between the anus and the scrotum.
It is of great importance in certain medical specialties such as urology, gynecology and
obstetrics, proctology, neurology, and muscular and fascial disorders, although the latter are
not covered by a single specialty. Physiotherapy is a closely related discipline that is
concerned with the problems of this complicated and complex area of our body.
The boundaries of the pelvic floor are: the anal triangle or posterior part containing the
anal canal, the ischiorectal fossae on each side, and the external anal sphincter; the urogenital
triangle or anterior part containing the external genitalia and terminal portions of the
urogenital ducts; the inferior side of the pelvis is closed, but the anal canal, urethra and, in
women, the vagina, pass through it.
The posterior part is closed by the pelvic diaphragm, and the anterior part of the inferior
part of the pelvis is closed by the urogenital diaphragm.
The two levator ani muscles and the two coccygeus muscles form the pelvic diaphragm
and close the narrow inferior part, or the pelvic outlet, forming a large funnel. The pelvic
diaphragm divides the pelvic cavity into two parts: the superior part containing the pelvic
viscera and the inferior part, called the ischiorectal fossa, containing fat.
The urogenital diaphragm is a thin sheet of striated muscle that lies between the two faces
of the pubic arch lining the anterior inferior part or the pelvic outlet where the most anterior
and the most posterior fibers follow a transverse course (transversus muscle), while the
medial fibers surround the urethra (external urethral sphincter muscle).
The muscles of the pelvic floor or perineum are: the external anal sphincter, the levator
ani, the coccygeus muscle, the bulbospongiosus muscle, the ischiocavernosus muscle, the
urethral sphincter, the superficial transverse muscle, and the deep transverse muscle.
The most important ones and the internal obturator muscle because of its important
relationship with the perineum and referred pain [3,4,5] are described below.
Levator ani muscle
Location: Posterior perineum. Consists of the puborectalis, pubococcygeus,

iliococcygeus, and levator prostatae muscles.
Insertions: Into the descending and horizontal rami of the pubic bone and into the
anococcygeal raphe.
Innervation: Pudendal Nerve and S2-S3-S4.
Action: As pelvic diaphragm and as elevator and constrictor of the anus.
Obturator internus muscle
Location: Interior and exterior of the pelvis.

Insertions: Inside into the inner faces of the obturator membrane, descending branch
of the pubis, and ischium; outside into the trochanteric fossa.
Innervation: Main branch of the sacral plexus.
Action: External rotator of the thigh.
Deep transverse perineal muscle
Location: Dorsal part of the urogenital diaphragm.

Insertions: Outside into the posterior surface of the ischial pubic ramus; inside into
the anterior part of the median perineal aponeurosis.
Innervation: Dorsal nerve of the penis.
Action: compressor of the urethra as part of the urogenital diaphragm. Contributes to
erection.
Ischiocavernosus muscle
Location: In the perineum.

Insertions: At the back into the face of the ischium and ischial pubic ramus; in the
front into the root of the corpus cavernosum.
Innervation: Pudendal Nerve.
Action: Erector of the penis.
Bulbospongiosus muscle
Location: In the anterior perineum.

Insertions: At the back into the median raphe; in the front into the superior aspect of
the bulb and the fibrous capsule of the dorsal aspect of the cavernous body.
Innervation: Pudendal Nerve.
Action: Accelerates or propels urine and semen.
External anal sphincter muscle
Location:
-Subcutaneous part: surrounds the anal canal, lacks bony attachments.
-Superficial part: perineal body.

-Deep part: surrounds the anal canal, lacks bony attachments.
Insertion: Coccyx
Innervation: Inferior rectal nerve and perineal branch of S3.
Action: Together with the puborectalis muscle it forms the voluntary sphincter of the
anal canal.
Coccygeus muscle
Location: In the posterior perineum.

Insertions: On the outside into the ischial spine and sacrociatic ligament; on the
inside into the margin of the coccyx.
Innervation: Coccygeus.
Action: Uncertain.
3. Anatomical-Clinical Correlation
After the initial studies by Travell and Simons, Dr. Anderson and his team at Stanford
University pioneered the study and detailed analysis of the pelvic floor muscles, their TrPs,
and the symptoms of each one of them. Obviously, in many cases these symptoms overlap
and it will be up to us to uncover this to be able to make an accurate diagnosis and take the
most appropriate therapeutic measures [1, 2, 24].
3.1. Internal TrPs of the Pelvic Floor, Typical Referred Pain, and
Resulting Symptoms
Levator Ani Muscle

Superior or puborectal portion
Most important location of TrPs in males.

Responsible for pain in the head and body of the penis. Probably caused by a TrP of
the levator prostatae (in our experience).
Sensation of fullness and pressure in the prostate.
Pain referred to the urethra and the bladder.
Pain or discomfort in the lower abdomen.
Increased urinary frequency and urgency.
Inferior portion
Pain referred to the perineum and the penis.

Middle portion, iliococcygeus muscle
Pain referred to the lateral wall, perineum, and anal sphincter.
Posterior portion
Sensation of a golf ball in the rectum.

Pain during and after ejaculation.
Pain after defecation.
External anal sphincter muscle
Pain in the anus.

Pain in the anterior part of the pelvis close to the pubis.
Pain in the posterior part of the anal sphincter.
Tingling and burning in the anal area (in our experience).
Coccygeus muscle
Pain around the tailbone.

Pain in the gluteus maximus.
Pain during bowel movements.
Intestinal fullness.
Anal pressure and pain, and sensation of a golf ball in the rectum.
Internal obturator muscle
Pain referred to the hip.

Vulvar pain.
Urethral pain in women.
Pain in the entire pelvic floor.
Sensation of a golf ball in the rectum.
May simulate a pudendal nerve entrapment (in our experience), and since the nerve
and the muscle are intimately related, palpation of the area causes a burning and
intense pain.
Bulbospongiosus and ischiocavernosus muscles
Pain in the base of the penis and perineum.

Pain in the ventral aspect of the penis (in our experience).
3.2. External TrPs of the Pelvic Floor, Typical Referred Pain, and
Resulting Symptoms
Quadratus lumborum muscle
Inguinal pain.
Pain in the lower abdomen.
Pain referred to the hip.
Low back pain.
Iliopsoas muscle
Low back pain.

Inguinal pain.
Pain in the front of the leg.
Rectus abdominis muscle
Pain radiating to the prostate area.

Pain inside the penis.
Pain in the lower abdomen.
Low back pain.
Abdominal oblique muscle
Pain radiating to stomach.

Pain radiating to ribs.
Inguinal pain.
Testicular pain. This is a cause of testicular pain that is often overlooked.
Figure 2. Pyramidalis muscle.

Pain in the bladder and urethra.

Erectile dysfunction.
Pain around the pubic bone.
Pain referred to the sacroiliac joint, buttock and hip that increase when standing and
sitting.
Pinched sciatic nerve pain with neurological compression symptoms.
Gluteus maximus, medius, and minimus muscles
Pain traveling down the leg.

Testicular pain.
Pain around the tailbone.
Pain in the sacrum.
Pain in the hamstrings.
Pain in the pelvic girdle.
Pain in the buttocks.
4. DEFINITION oF tHE TRIGGER

POINT (TrP) [21,22]
A TrP is a tiny area (it palpates like a grain of "crispy rice") with a diameter between 5
and 10 mm; it is highly irritable, located inside a muscle, rigid (taut band) on palpation, has a
restricted stretching amplitude, and shows noticeable weakness. There is no atrophy or
fibrosis and normally there is no neurological involvement, although there may be; in fact,
there usually is neurological involvement to a greater or lesser extent when the TrP has been
evolving for a long time.
It causes a decrease in the elasticity of the muscle involved and its fascia. With chronicity
it causes shortening of the muscle and of adjacent structures.
4.1. Types of Trigger Point
Active TrPs: these are painful without stimulation. They are always sensitive; the
patient experiences them as constantly painful spots. The pain increases on palpation,
pressing, mobilizing, and stretching the muscle.
Secondary TrPs. These usually appear in response to the contraction of agonist and
antagonist muscles that attempt to compensate for the injured muscle.
Latent or satellite TrPs. These develop within the reference area of the original TrP.
They are only painful on palpation and when activated they can behave as active
TrPs.
5. Etiology and Mechanisms of

Production of the Lesion
Chronic muscle tension patterns since childhood (sexual abuse [96], chronic
constipation [95], dance training, stress, etc.).
Small repeated traumas such as constipation, recurrent urinary tract infections,
impact sports or sports with risk of perineal injuries, even if no injury occurs
(bicycling, jogging, horseback riding, athletics, gymnastics, ballet, etc.).
Small acute injuries when practicing sports.
Direct physical trauma as a consequence of bicycling, labor, or urological or
gynecological surgery.
Inflammation of the pelvic organs: prostatitis, cystitis, urethritis, endometriosis,
vaginitis, proctitis, hemorrhoids, or anal fissures
Pain referred from other muscle groups, viscera, or nerves.
6. Epidemiology
The condition is very common, but often it is not diagnosed as such. Of 283
consecutive admissions to a pain clinic, 85% were diagnosed as suffering from
myofascial syndrome somewhere in the body [81]. The highest incidence is found
among people between 30 and 50 years old. Latent TrPs become more frequent with
increasing age and decreasing physical activity.
In a multicenter study done in urological outpatient centers of 28 hospitals in Italy
with 5,540 patients, Bartoletti et al. found that 746 of them had chronic pelvic pain.
The prevalence of the syndrome was 13.8% and the estimated incidence was 4.5%.
The syndrome is closely related to among others lifestyle, diet, smoking, sexual
dysfunction, and anorectal disorders. Therefore, this phenomenon is much more
significant than expected [95].
Other authors have found results along the same lines [97, 99, 101].
The relationship between sexual dysfunction and pelvic floor muscle problems
(prostatitis) is very common and frustrating for the quality of life of patients, both
men and women [102,103].
A study by Krieger in 2004 on the classification, epidemiology, and implications of
chronic prostatitis in the U.S., Europe, and Asia is worth reading, since it clarifies a
number of uncertainties such as its actual frequency: it affects 2-10% of adult men
and 15% suffer symptoms of prostatitis at some point in their lives [104].
It is more common in women than in men.
It is also more common in patients who perform tasks involving repetitive use of the
muscles of the pelvic girdle, pelvic floor, and lower limbs, and who must also,
because of the nature of their work, adopt incorrect, antiphysiological, or non-
functional postures.
Ninety-five percent of men diagnosed with chronic prostatitis do not show evidence
of inflammation or infection [112,113].
7. Physiopathology
The physiopathology is largely unknown.
The most widespread theories are:
1. The energy crisis theory: This concept was developed to explain four significant
facts: first, the absence of action potentials of the motor unit in the taut band of a TrP
when the muscle is at rest; second, the fact that TrPs are activated by muscle strain;
third, the sensitization of nociceptors in the TrPs; and fourth, the effectiveness of
almost any therapeutic technique that leads the muscle from a shortened state to its
proper length [73, 74].
2. Theory of dysfunctional muscle spindles: Hubbard and Berkoff concluded in an
interesting paper that the EMG activity of TrPs was caused by dysfunctional use
[77].
3. Pain-spasm-pain cycle hypothesis: This old concept does not stand up to
experimental evidence, be it from the physiological point of view or from the clinical
point of view [75, 76].
TrPs are thought to arise from a neuromuscular dysfunction and to evolve into well-
defined histological lesions.
Any trigger can activate pathogenic mechanisms which give rise to the fascia, the muscle
it contains, and sometimes other neighboring flexible and elastic connective tissues losing
their own elasticity and the ability to glide between the different layers, which is vital for their
proper function.
As a consequence, the fascia and muscle shorten and ache, and generate in an area of the
muscle a taut band within which there is a hyperirritable point, the so-called "Trigger Point".
When not treated adequately and early, this creates a situation that can be compared with
the wave that forms when you throw a stone into the water: the initial active spot creates
hypomobility and dysfunction in adjacent tissues and viscera which, in the end, is sometimes
greater than the problem that caused it. For this reason, myofascial dysfunction is sometimes
quite distant from the point where it originated.
Myofascial TrPs Cause Chronic Pelvic Pain by Three Mechanisms
Through local tension around the affected organs and referred muscle patterns.
The striated muscles of the pelvic floor adhere closely to the visceral structures (urethra,
bladder neck, prostate, vagina, and rectum) for support and sphincter control.
Because the afferent nerves of the viscera and deep muscles connect to the medial
thalamus, they cannot locate noxious stimuli as do the nerves of the skin, which go from the
lateral thalamus to the somatosensory cortex.
Therefore, patients with active TrPs and pelvic floor spasms do not perceive that their
symptoms originate in the pelvic muscles.
They also experience varying degrees of emotional stress.
Viscerosomatic and somatovisceral reflexes.
The effect of visceral pain on somatic structures was shown by Vecchiet et al. (1989) [7]
and by Giambernardino et al. (1994) [8]. They found that between 30 and 64% of patients
who had suffered repeated episodes of renal colic experienced lumbar muscle hyperalgesia
years after the original pain.
The second group postulated that colic pain produced plastic neural changes in spinal or
supraspinal levels that were perpetuated after the visceral impulses ceased.
These studies may actually have found myofascial TrPs created by visceral pain via the
viscerosomatic reflex. This repetitive pain model may be applicable to any inflammation of a
pelvic organ.
Central sensitization
TrPs are not only sources of pain, but can also sensitize neurons of the CNS, thus leading
to a more intense neuropathic pain that is resistant to treatment.
A review of the neurophysiologic bases of pain [9] suggests that afferent nerve branches
in the spinal cord join with many dorsal horn cells in many upper, lower, or contralateral
segments of the spinal cord.
Taken together, the nerves of muscles, organs, or skin may converge in the dorsal horn
neurons and interfere with each other at supraspinal levels as a second-order neuronal
pathway that is in close contact with the brainstem and the thalamus on their way to the
cerebral cortex [10].
This interaction prevents a normal and coordinated communication between the organs.
Thus, any damage in dorsal horn neurons and thalamic cells, which are the heart of the
nervous communication system, may cause a general dysfunction.
Its normal activity is altered by chronic pain stimuli from the peripheral nerves that join
with them.
These harmful impulses can have many causes: active trigger points, visceral pain,
inflammation of the skin, etc.
And when they reach the cells in the spinal dorsal horn via C-fibers, neuropeptides are
released which produce physical, chemical, and genetic changes that facilitate abnormal
connections [11].
These plastic changes may alter pain perception in a variable way and cause pain by non-
painful stimuli (allodynia); the pain can also be spontaneous, intensify (hyperalgesia), extend,
or increase in duration, thus contributing to the worsening of the initial disease [11].
What begins as myofascial, visceral, or superficial may, with a sufficiently noxious
stimulus, be transformed into neuropathic pain affecting a wider area and more organs [7, 8,
9].
If the dorsal horn cells remain in a state of sensitization, the initial pain may be
reactivated by a noxious stimulus that reaches them from an organ that shares their nervous
fields.
The sensitivity of these cells may be influenced by many changing factors: depression,
hormonal changes during menstruation, sleep alterations, diet, etc. [12].
Pathophysiological Considerations Related to the Treatment
Can these nerve disorders or sensitized neurons return to normal?

We can treat the trigger points, but can we treat the newly established reflex patterns or
sensitization of the CNS?
Gracely et al. [13] suggest that changes in the central process cannot be sustained without
the continuation of the painful focus. In their study, when they produced an anesthetic block
of a painful point near the elbow, chronic pain in the distal part of the arm and the hand
disappeared.
Other authors, such as Koltenburg et al. [14], Cohen and Arroyo [15], Bach et al. [16],
and Bonica (1990) show that the central processing mechanism reverts to normal when
nociceptor activity is reduced to below critical levels.
Thus, if we provoke a block of the sensitized nerves and achieve a symptom-free period,
we make recovery possible since there are no noxious stimuli at that time.
8. Perpetuating Factors
These do not receive sufficient attention. If they are not eliminated, treatment will not
last.
They are also predisposing factors. The "overload" factor of the muscles is constant.
Elimination may lead to the disappearance of active TrPs.
8.1. Mechanical Stress
Lower extremity dysmetria (LED). If one lower extremity is shorter than the other, this
can cause pelvic tilt while standing, lead to compensatory scoliosis, and to a perpetuation of
the TrPs. This can be corrected with heel elevation. It is a key perpetuating factor. LED is
strongly associated with back pain. It is worth to mention not only dysmetria of the LE but
also changes in foot support that require correction with arch support and that can also create
perineal dysfunction, especially when associated with risk factors such as sports or a standing
profession. The impact that is cushioned at the pelvic floor is transmitted by the legs from the
supporting base, which is the foot, while the lower limb is merely the transmitter of the
impact [65,66].
8.2. Postural Dysfunctions and Abnormalities
Dysfunction of the Sacroiliac Joint, the Sacrococcygeal Joint, and the

Lumbosacral Hinge May be Aggravating Causes for the TrPs of the
Pelvic Floor [53]
The TrPs in the levator ani and coccygeus are perpetuated by postural tension caused by
inadequate furniture, defective postures (both standing and sitting), overuse of muscle groups,
prolonged immobility or sitting, and repetitive overload [67,68,69]. This leads in most cases
900 F.. Itza Santos, D.
D Zarza, L. Serra Llosa et al.
a
too hypotonia off the subumbilical abdominnal girth and a hypertonia off the thoracic diaphragm
thhat generates hyperpressuree on the pelvvic diaphragm m, which respoonds with hyppertonia or
hyypotonia; bothh situations are a possible but b in either case harmfull, because theey produce
puudendal neuroopathy by com mpression in the first case and by overstretching in the second
caase. In the lattter case it is allso an aggravaating and/or trriggering factoor for genital prolapse
p in
w
women.
In an intereesting article, Slocumb saidd that other coeexisting diseasses such as ovvarian cysts
orr pelvic adhessions do not prevent
p a satissfactory responnse to local innfiltration of the
t TrPs of
thhe levator ani, coccygeus, orr in scars of thhe vaginal cufff after hysterectomy [71].
King et al defined a typpical posture of patients with w chronic pelvic
p pain coonsisting of
loordosis and anterior pelvic tiilt, which occuurs in 75% of the cases seenn [72] (Figure 3).
Fiigure 3.
8.3. Nutritional Disorde

ers [78, 79]]
The water--soluble vitam

mins B1, B6, B12,B folic aciid, vitamin C, and the tracce elements
caalcium, iron, and
a potassium m play a role inn myofascial pain syndrome.
Vitamin C,, which is parrticularly impoortant in this syndrome, is an essential co-factor
c in
eiight different enzymatic reaactions such as a norepinephhrine and serootonin synthessis, both of
w
which are invoolved in the central
c modullation of painn transmissionn. It is also innvolved in
coollagen syntheesis and aminoo acid degradaation. Collagen makes up onne fourth of tootal protein
inn organic tissu
ues, and thereffore vitamin C deficiency leeads to musclee and ligamennt disorders
thhat may eventuually cause or perpetuate TrrPs [82].
There are two levels off vitamin defiicit: insufficieency, which requires
r somee metabolic
addjustment by the organism m, and deficieency which iss a gross funcctional impairrment with
serum levels below the limit accepted as normal and associated with full-blown clinical
disease.
Prevalence
In a hospital-based study of 120 patients, 105 (88%) had low levels of one or more
vitamins out of eleven, and 60 (50%) had low levels of two or more vitamins.
Folic acid was low in 45% of the patients, but only 38% had clinical manifestations [83].
Toxicity
Fat-soluble vitamins A, D, and E have a much greater toxicity than the water soluble B
complex vitamins.
Hypervitaminosis A can cause bone and joint pain and a severe throbbing headache,
which can be confused with myofascial symptoms related to vitamin A deficiency.
8.4. Metabolic and Endocrine Disorders
Hypothyroidism, which may be subclinical [84].

Growth hormone deficiency.
Hyperuricemia.
Obesity.
Hormonal changes: menopause.
8.5. Psychological Factors
Stress [93].
Hyper-responsible personalities.
Depression.
Anxiety-depression syndrome [93].
8.6. Chronic Infections and Infestations
Chronic prostatitis. Interstitial cystitis.

Repeat cystitis.
Oophoritis, salpingitis.
8.7. Other Factors
Sleep disturbance [85, 86, 87]. This is a very important factor because if the patient
does not recover at night, chances of developing or perpetuating TrPs are very high.
Pinched nerve (peripheral entrapments and radiculopathies). There is a significant

correlation between its existence and the existence of TrPs [88, 89, 90, 91].
Exhaustion or generalized fatigue.
Total or partial abrupt cooling.
Hemorrhoids, anal fissures (both the pathology and its surgical correction).
Endometriosis.
9. Diagnosis
Trigger points of the LE are deceptive and often go undetected. The discomfort they
produce often leads to diagnostic errors because it is thought to stem from a different source.
To determine the cause of musculoskeletal pain, it is much safer to let oneself be guided
by other features than the location of the discomfort and the hypersensitivity.
Diagnosis of myofascial pain is done by checking the clinical history, pain measurement,
manual/digital examination of the musculature, and electromyographic findings [44].
9.1. Clinical History
Chronic or repetitive acute muscle overload is always involved in the onset of pain and
always contributes to chronic pelvic pain.
The intensity of the pain depends on the posture or movement, and can be continuous
when severe.
Pain (anorectal, perineal, in the penis, etc.), local dysfunction (muscle weakness due to
hypertonia, loss of coordination), sleep disorders, etc.
The referred pain for each muscle was already discussed in the section "anatomical-
clinical correlation" above.
The patients history might reveal a possible beginning in the prostate, progressing with
pain in the urethra followed by increased urinary urgency and frequency, anal pain, lumbar
pain, headaches, anxiety, stress, fatigue, and finally sexual dysfunction and depression.
9.2. Measuring Pain
Pain can be measured with the frequently used visual analog scale (VAS).
The McGill questionnaire is reliable and valid to measure pain as a multidimensional
experience because it assesses sensorial and affective aspects, as well as the intensity of pain.
The pain diagrams originally described by Travell and Simons are very useful because
they accurately reflect the location and extension of the pain.
9.3. Physical Examination
TrPs are identified through palpation, first superficial and then deep. In addition to the
TrPs, the basal tonus of the thoracic diaphragm, the subumbilical abdominal wall, the pelvic
floor, and lastly, the mobility and texture of the connective tissue in all these areas should be
assessed. Finally, the standing posture must be assessed (symmetry of the folds, breathing,
bone reference points, etc.).
Deep palpation: When exploring the area in search for a TrP and the taut band
around it, the following may be found: hyperirritability, immobility, tenderness,
edema, tension, and muscle contracture.
The jump sign is typical, and constitutes a valuable indication of a TrP. All Berger
tender points should be palpated (Figure 4).
Figure 4.
The administration of a muscle relaxant two hours before enables a more accurate
detection of active TrPs because it temporarily reduces the pain of secondary and
satellite TrPs.
Diagnostic dry needling. A needle is inserted into the TrP, causing a local twitch
response (spasm). Very typical.
Local anesthetic block. Local and referred pain disappear; as we shall see, this
procedure can also be therapeutic.
Pressure using an algometer. To measure the pain pressure threshold of the muscles
having TrPs.
9.4. Electrophysiological Studies
The electrodiagnostic features of the TrPs were first described by Weeks and by Travell
in 1957. Hubbard and Berkoff reported a similar electrical activity in myofascial TrPs and
according to them only high-frequency spike potentials are characteristic [77].
Later, Simons and Hong detected another component in the form of low-amplitude noise,
which was always present. This noise was called spontaneous electrical activity [29, 94].
In our experience, it is common to find an increased basal muscular activity at rest which
is related to the pathogenesis of the process; this can be quantified by averaging the
turn/amplitude obtained in electromyographic analysis. Essentially, the number of turns of the
EMG signal is measured during a unit of time, and the mean amplitude of the turns obtained
during this period; the values are then compared to those obtained with healthy subjects.
Basically, the test consists of recording the EMG activity in various muscle sites
(between 6 and 10), preferably in the area halfway between the motor point and the tendon.
Each point represents the automatic analysis of a period or "epoch". Between 20 (minimum)
and 30 tests are done. Under normal conditions, the points are distributed in a "cloud" shape,
where 95% of the obtained points are found. When at least 10% of the points are outside the
cloud, this is considered pathological.
This tool can be useful when assessing the progress of patients after several therapeutic
interventions [119,120,121].
Figure 5.
9.5. Thermography
Thermographically, a TrP appears as a small area that has a temperature between 0.6 and
1C higher than the surrounding tissue or its contralateral area [109,110,111].
10. Differential Diagnosis

The three most common musculoskeletal disorders that require special attention are
myofascial pain, fibrositis or fibromyalgia, and joint disorders.
For none of the three disorders there are radiological or laboratory tests that help to
strengthen the diagnosis.
Therefore, diagnosis is made based on a thorough clinical history and a detailed physical
examination, especially of the muscles.
Too often these three pathologies are misdiagnosed because the clinical history and
physical examination are not carried out systematically.
To avoid this situation, the examiner should know exactly what to look for and develop
the manual dexterity to find it. The examination should be guided by a presumptive diagnosis
[117].
Confirmatory Findings of Myofascial Syndrome
Local twitch response induced by palpation or by inserting a needle through a TrP,

and which is evidenced by detection of movement by sight, palpation, or ultrasound
imaging.
Referred pain patterns for each muscle.
Motor endplate noise when an EMG needle is inserted into the TrP.
Inconveniences When Palpating a Trigger Point
Obesity.
Interposed muscles.
Interposed aponeurosis.
Tense and deep subcutaneous tissue.
Lack of palpatory skill.
11. Treatment
The fundamental principle of therapy is based on myofascial release through inactivation
of the TrPs and muscle re-education.
Pain of musculoskeletal origin is more likely to be controlled if its cause is identified and
corrected.
Effective treatment is difficult to attain and relatively slow. A multidisciplinary team is
required for chronic pain syndromes with complications.
According to a study by Giubilei et al. [118], aerobic exercise seems to be beneficial for
the recovery of patients with chronic pelvic pain. This must be evaluated in each case by the
professionals who treat the patient; in early stages of treatment it is usually harmful.
Recommendation of exercise must be individually tailored to each case.
11.1. Medical Treatment
Physical trauma during bicycling, labor, or urological, gynecological, or

colpoproctological surgery.
Inflammation of pelvic organs or structures: prostatitis, cystitis, urethritis,

endometriosis, vaginitis, proctitis, hemorrhoids, or anal fissures.
11.1.1. Treatment Of Chronic Bacterial Prostatitis

Treatment with antibiotics: when, how, for whom?
Repetitive prostatic massage: when, how, for whom? According to Dr. Felicianos
Manila protocol [115,116].
Intraprostatic injections: when, how, for whom? According to Dr.Guercini's protocol
[114].
11.1.2. Infiltration with Local Anesthesia.

In a single-blind study comparing lidocaine, botulinum toxin, and dry needling to
inactivate TrPs, Kamanli et al showed in 29 patients with myofascial pain that lidocaine
injection is faster, more effective, and causes less discomfort than dry needling, and is more
cost-effective than botulinum toxin [25]. Many other authors reach the same conclusions,
especially regarding postoperative discomfort and greater therapeutic efficacy [45, 46, 64].
On the other hand, Langford et al injected a mixture of lidocaine, bupivacaine, and
triamcinolone to treat TrPs in the levator ani muscle in 18 women. They obtained
improvement in thirteen patients after the first injection (72%). Six women (33%) became
completely pain-free. The authors were surprised by the high efficacy of the treatment and the
underutilization by other professionals [26].
However, there is no evidence that corticoids combined with anesthetics improve the
clinical response compared to local anesthetics alone [37]. Moreover, it is known that the
repeated use of steroids can cause degenerative lesions and even rupture of the muscles [38,
39].
11.1.3. Corticosteroid Infiltration in Areas with Enthesopathy or

Tendinitis.
Since myofascial pain syndrome involves muscle shortening, there will obviously be
abnormalities in the areas of muscle insertion, be it tendinitis or enthesopathies. Kang et al
used transanal infiltration with lidocaine and triamcinolone every two weeks for a maximum
of three sessions. The mixture was injected in the most tender areas. There was significant
improvement at 36 months of follow-up.
The authors concluded that the procedure is sufficiently simple, safe, and effective to be
recommended as a first-line therapy [28].
11.1.4. Infiltration with Botulinum Toxin

In Spain, we work with Botox or Botulinum toxin type A: it is a neurotoxin produced by
Clostridium Botulinum. It works by inhibiting the release of acetylcholine at the
neuromuscular junction, which results in the chemical denervation of the latter, thus
paralyzing the treated muscle.
Botulinum toxin has been recognized by many authors as a good treatment for myofascial
syndrome, and is used successfully in any area of the body [54]. It reduces the tone of
contractured muscles [108].
In a pilot study, Sherin et al. injected 12 women suffering from chronic pelvic pain
associated with spasm of the levator ani with Botox. Their results were promising, since they
obtained alleviation of pain and a reduced hypertonicity [55, 56].
Other authors recommend the toxin only when other simpler measures, such as dry
needling, have failed [57, 58, 59, 60, 61].
However, Gbel et al conducted a prospective, randomized, double-blind study about the
safety of this treatment, and reported good tolerance, fast resolution of side effects, and
significant improvement of pain 46 weeks after treatment [62].
Zermann et al. observed that pelvic and prostatic pain are accompanied by motor and
sensory disorders, which led them to hypothesize that prostatic pain stems from a changed
processing of afferent and efferent information in the central nervous system. They concluded
that the injection of Botox around the urethral sphincter can lower its tone by blocking
acetylcholine and interrupting negative efference from the CNS, leading to pain relief and
improvement of the symptoms [63].
11.1.5. Acupuncture and Electroacupuncture.

In their study on acupuncture, Chen and Nickel concluded that this is a safe, effective,
and lasting method to improve symptoms and the quality of life of patients with pelvic pain.
As a neuromodulatory and minimally invasive treatment, this is an option when traditional
therapies fail [105,106,107].
11.1.6. Scar Treatment

Abdominal, perineal, or lumbosacral scars can cause abdominal pain or pelvic pain and
limit the mobility of muscles and fascias. Kuan et al treated 221 painful scars with a mixture
of 0.5% bupivacaine, 2% lidocaine, and betamethasone infiltrated into the fibrous tissue, and
obtained a high rate of success. The pain had disappeared in 86.5% of the patients after three
months of follow-up [27]. The procedure is supplemented with specific physical therapy
techniques, both manual and instrumental (hyperthermia, laser, ultrasound).
11.2. Physiotherapeutic Treatment
11.2.1. Physical Therapy

Physical therapy consists fundamentally of analytical and global techniques: massage,
stretching, release of TrPs by acupressure and dry needling, the release of mobility limitations
in the fascias (myofascial induction techniques), and craniosacral rhythm regulation in cases
with scars; when initial assessment determines a need, hypertonicity of the diaphragm and the
abdominal musculature as the main regulators of the transmission of intra-abdominal pressure
should be treated.
Time is a critical factor. The release of fibers is a slow process.
Clinical experience shows that slowly sustained stretches are much more effective than
rapid stretches. Unfortunately, as soon as the muscles relax, the sarcomeres return to their
initial state unless something more is done. We must continue with post-isometric relaxation
or contract-relax. Contraction alone is an inadequate treatment. Gentle contraction must
follow (10% of maximum). This would be contract-release or post-isometric relaxation and
release [21].
For the rehabilitation of the short pelvic floor, Fitzgerald and Kotarinos recommend ten
weekly one-hour sessions, and have been generally successful with the following regime [35,
36]:
1. Avoiding activities that may exacerbate the problem, such as Kegel exercises,
abdominal exercises, and wearing tight clothes.
2. Correcting poor posture and recommending other more common ergonomic postures.
3. Detecting anatomical abnormalities such as a small pelvis.
4. Treatment of connective tissue disorders, especially panniculitis.
5. Treatment of abdominal and perineal scars that produce restrictions on normal
mobility.
6. Treatment of extra-abdominal TrPs.
7. Stretching exercises of the abdominal muscles.
8. Release of the pelvic floor TrPs by means of pressure, post-isometric relaxation,
proprioceptive neuromuscular facilitation, and reciprocal inhibition.
9. If required, anesthetic infiltration of the TrPs.
10. Pudendal blocks, if required.
11. Home maintenance programs of stretching exercises for the abdominal muscles and
relaxation of the pelvic floor in a squatting position and pushing the knees (Figure 6).
Figure 6. Adductor (pctineo): Adductor (pectineus), Glteos: Glutes, Iliopsoas: Iliopsoas, Caudrado
Lumbar: Quadratus Lumborum, Piriforme y rotadores laterales: Piriformis and lateral rotators, Recto
abdominal: Rectus abdominis, Pelvis: Pelvis.
11.2.2. Release Methods

The immediate elongation of the muscle promotes equilibrium with respect to the length
of the sarcomere; when this is done slowly, it helps to reconfigure the new sarcomere length,
which thus tends to stabilize.
In any case, complete relaxation of the patient is a prerequisite for effective release.
11.2.2.1. Release through Pressure on the TrP

This consists of applying a gentle and gradually increasing pressure on the TrP until an
increased tissue resistance is found by the finger.
This maneuver normally causes bearable pain. Pressure should be maintained until the
clinician notices a reduction in the tension under the palpating finger.
At this point, the finger increases the pressure enough to reach the next barrier: the finger
follows the tissues that are being relaxed. Again, the clinician sustains a gentle pressure
until the tension yields under the finger [3,22,24].
Sexual dysfunction is common among patients with refractory pelvic pain; application of
myofascial release and paradoxical relaxation is very helpful in the treatment of pelvic pain,
urinary symptoms, libido, ejaculatory pain, erectile dysfunction, and postejaculatory pain [2].
Weiss reported successful outcomes in 52 patients with interstitial cystitis and urethral
syndrome treated with manual therapy. About 70% and 83%, respectively, experienced
moderate or marked improvement. Electromyographically a decreased muscle tone was
observed. Duration of the symptoms had been 614 years [51].
Acupressure of the levator ani and obturator internus muscles
Digital examination in men digital examination in women
11.2.2.2. Release through Dry Needling

This TrP release method is increasingly popular among physical therapists and is also
practiced by physicians. Its therapeutic usefulness has been recognized by such prestigious
organizations as the Cochrane Collaboration [43].
On the other hand, the false popular and professional belief that Chinese acupuncture and
medical acupuncture or dry needling are the same thing leads to error and confusion.
However, there is a 71% overlap in the location of traditional acupuncture points and dry
needling points [40, 41, 42].
Gunn et al. developed a method for deactivation of TrPs called intramuscular stimulation,
which involves introducing a needle into the TrP as is done in dry needling [48]. This can be
combined with electrical stimulation through the inserted needle.
A Korean study from 2007 seems to confirm the results of Gunn et al. and highlights the
better results obtained with this technique compared with infiltration of 0.5% lidocaine [52].
11.3. Psychological Treatment
Relaxation techniques: Jacobsons progressive relaxation, Wises paradoxical relaxation,

yoga, meditation, etc.
Dr. Wises paradoxical technique combined with point release is proving to be a more
effective method to alleviate pain and urinary dysfunctional symptoms than traditional
methods. Thus, marked improvement is achieved in 72% of cases [1, 23].
12. Evolution and Prognosis

Clear signs of improvement are seen in most cases after three or four months of treatment
with medical and physical therapy, with two weekly one-hour sessions, a daily program of
specific stretches at home, body relaxation techniques, and stress management.
Up to two years may be necessary for a stable and permanent improvement of myofascial
syndrome.
Conclusions
"Evidence based medicine is not cookbook medicine with a book where all formulas
can be found. External clinical evidence can inform but can never replace individual clinical
expertise, and it is this expertise that decides whether the external evidence is applied to the
individual patient at all. David Sackett said this, and we must apply it to a complex problem
that results in a large number of chronic disabilities, decreased quality of life, and much
suffering among those who experience this condition.
The additive effect of patterns of constant pelvic tension, trauma, inflammation, or pelvic
organ disease can overload the muscles and stimulate the development of TrPs and hypertonia
of the pelvic floor.
Therapy should be aimed at total eradication of noxious stimuli transmitted from the
body surface, viscera, trigger points, or mechanical alterations of the body to the sacral spine
to allow periods free of noxious stimuli.
We must always keep in mind that a chronically shortened and hypertonic muscle will
asphyxiate, catabolites will accumulate inside, and in time this can lead to degenerative
histological changes. This is why the longer the duration of the dysfunction, the worse the
prognosis for the muscle, the nerve, and the fascia. The key factor is time (one of the
diagnostic errors is precisely not giving importance to myofascial dysfunction in very early
stages and with very mild symptoms).
From the above, we should also conclude that early physiotherapy and neurotherapeutic
treatment of postoperative scars is important, to prevent the development of myofascial
dysfunction.
It should also be noted that patients with long-lasting myofascial pelvic floor dysfunction
manifest complex sets of psychological symptoms (anxiety, depression).
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Chapter IV
Hormonal Modulation of
Genitourinary Pain
Anna P. Malykhina*1 and Gina M. Northington2

1
Division of Urology, Department of Surgery,
University of Pennsylvania, Glenolden, PA, U.S.
2
Division of Urogynecology and Pelvic Reconstructive Surgery,
Department of Obstetrics and Gynecology, University of Pennsylvania,
Philadelphia, PA, U.S.
Abstract
Genitourinary pain is a common clinical problem that severely affects the quality of
life in women and contributes to chronic pelvic pain (CPP). The American College of
Obstetricians and Gynecologists (ACOG) has defined CPP in women as localized non-
cyclic pain of longer than 6 months in duration that leads to a loss of function.
Approximately 25-35% of laparoscopies and 10-15% of hysterectomies in the US are
performed to identify a source of CPP.(references needed Farquhar CM and Steiner CA
Obstet Gynecol 2002: 99:229; Howard FM Obstet Gynecol Surv 1993; 48: 357) The
range of disorders characterized by CPP is broad and includes gastrointestinal disorders
(diverticulosis, inflammatory bowel disease, irritable bowel syndrome, etc.), urologic
disorders (interstitial cystitis, urethral syndrome, chronic calculi, etc.), and gynecologic
disorders (endometriosis, vulvodynia, dyspareunia, hydrosalpinx, adhesions, etc.). Many
of these disorders do not have discrete pathologic findings that are treatable. The limited
understanding of the causes and underlying mechanisms together with the lack of
demonstrable pathologic findings and multiple co-morbidities associated with chronic
pelvic pain in women suggests a neuroinflammatory component to the development of
CPP in women. The presence of specific neuropathic symptoms (burning and tingling
* Corresponding Author: Anna P. Malykhina, Ph.D., Division of Urology, Department of Surgery, University of
Pennsylvania School of Medicine, 500 S. Ridgeway Ave, #158, Glenolden, PA, 19036-2307, Tel. (office):
(267) 350-9606, Fax: (267) 350-9609, E-mail: Anna.Malykhina@uphs.upenn.edu.
110 Anna P. Malykhina and Gina M. Northington
pain, site specific allodynia) in patients with multidimensional pelvic pain makes CPP
disorders extremely difficult to cure.
The clinical approach to functional pelvic pain disorders often requires
multidisciplinary efforts for successful treatment and frequently includes input from
urologists, gastroenterologists, gynecologists, and psychologists. Because of this,
considerable interest has focused on identifying common etiologic pathways that result in
a multidimensional model of clinical phenotypes of chronic pelvic pain in women. One
emerging concept for the co-existence of clinical disorders with functional CPP includes
cross-sensitization within the pelvis due to shared neural pathways connecting different
pelvic organs. Cross-sensitization develops as a result of noxious stimulus transmission
from a diseased pelvic organ to an adjacent normal structure resulting in the development
of neurogenic inflammation and the occurrence of functional changes in previously
normal pelvic structures. Several animal models have gone through the initial testing to
mimic the co-morbidity of clinical diagnoses as well as to investigate the mechanisms of
multisystemic CPP.
This review summarizes the results of the latest clinical, translational and basic
science research efforts on the hormonal regulation of genitourinary pain. The cellular
and molecular mechanisms underlying CPP and associated with multiple pelvic pain
disorders are presented in comparison to clinical findings and observations. Clinical
phenotyping of patients with CPP has been recently proposed in an attempt to clarify
heterogeneity of these populations and to improve treatment by using individualized
targeted therapy. Future basic and translational research should be directed at developing
therapeutic approaches that target CPP as a multidimensional and complex entity which
is not just organ specific.
Introduction
Genitourinary pain is a possible symptom of many debilitating medical conditions of the
reproductive and urinary tracts and one of the components of chronic pelvic pain (CPP).
Chronic pelvic pain is a complex sensory modality that incorporates neurophysiology,
cognitive, and motivational factors in humans (60). The neural pathways in the central and
autonomic nervous systems involved in the transmission and processing of painful sensations
are influenced by these aspects. Genitourinary pain can originate from a primary abnormality
within a pelvic organ (or the pelvis itself), or it may be referred to adjacent visceral or somatic
structures. There is consistent evidence that having one type of chronic pain is associated with
a higher likelihood of having another (26). Women with more than one medical condition
may have greater pain than women with only one disorder (137).
Pelvic pain affects up to 2.5 million women (21) and is more common than migraine or
asthma (136). There are many causes of CPP in women as summarized in Table 1. Figure 1
depicts typical clinical phenotypes with considerable overlap of co-morbid pain disorders.
Gynecologic sources of pelvic pain emanate from the reproductive organs (uterus, fallopian
tubes, and ovaries) as well as the vagina, vulva, or clitoris (49; 97). Because gynecologic
conditions may account for 20 percent of cases of CPP (135), these disorders contribute
substantially to genitourinary pain in women and are likely regulated by ovarian hormones.
For the purposes of this chapter, we will focus on the most common causes of genitourinary
pain in women and summarize the results of both clinical and basic science research on the
modulation of such pain by ovarian hormones.
Hormonal Modulation of Genitourinary Pain 111
Table 1. Conditions associated with Chronic Pelvic Pain in Women
Gynecologic Conditions
Endometriosis
Adenomyosis
Vulvodynia/Vestibulitis
Pelvic inflammatory disease
Endosalpingiosis
Neoplasia of the reproductive tract
Dysmenorrhea
Adnexal cysts or masses
Urologic Conditions
Interstitial cystitis/Painful Bladder Syndrome (IC/PBS)
Urinary tract infection
Urethral diverticulum
Urethral syndrome
Neoplasia of the lower urinary tract
Urolithiasis
Gastrointestinal Tract Conditions
Irritable bowel syndrome
Inflammatory bowel disease
Diverticulosis/Diverticulitis
Chronic bowel obstruction
Chronic constipation
Celiac disease (Sprue)
Bowel ischemia
Musculoskeletal Conditions
Pelvic floor myalgia
Coccygodynia
Piriformis syndrome
Hernia
Abnormal posture
Fibromyalgia
Other Conditions
Neuralgia of the pelvic nerves (iliohypogastric, ilioinguinal, genitofemoral, or pudendal)
Prior pelvic surgery
Adhesions
Pelvic fracture
1. Clinical Phenotypes of Genitourinary Pain and

Co-Morbidity with Other Painful Disorders
1.1. Endometriosis
Endometriosis is a common painful gynecologic disorder occurring in 70-87% of women

with chronic genitourinary pain (1). This disease is characterized by the presence of
endometrial glands and stroma outside of the uterus on peritoneal surfaces of pelvic organs
and muscles. Multiple theories have been proposed regarding the etiology of endometriosis
including retrograde menstruation, lymphatic or vascular transport, or transformation of

coelomic epithelium into endometrial tissue (27). Irrespective of the pathogenesis, the cyclic
degeneration that occurs in the explanted endometrial tissue promotes a chronic inflammatory
process that results in chronic peritoneal irritation. Endometriosis is associated with many
distressing symptoms including pelvic pain, severe dysmenorrhea, dyspareunia and infertility
(27). It can be diagnosed in many women who are asymptomatic and have explanted lesions
discovered incidentally at laparoscopy or exploratory surgery. Despite numerous studies,
considerable controversy remains regarding the incidence, pathogenesis, natural history, and
optimal treatment of this disorder.
Interstitial
Cystitis (IC/PBS)
IC + IBS IC + V
Irritable Bowel IC+IBS+D

Vulvodynia (V)
Syndrome (IBS)
IBS+V+D
IBS+D V+D
Dysmenorrhea (D)
Figure 1. Clinical phenotypes and overlap of co-morbid disorders in women with chronic pelvic pain.
IBS - Irritable bowel syndrome, V - Vulvodynia, E - Endometriosis, D- Dysmenorrhea, IC - Interstitial
cystitis/Painful bladder syndrome.
The most common sites of endometriosis are the ovaries, anterior and posterior cul-de-
sac, posterior broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon
and appendix and round ligaments (41). Other less commonly involved sites include the
vagina, cervix, rectovaginal septum, cecum, ileum, inguinal canals, abdominal or perineal
scars, urinary bladder, ureters, and umbilicus (122). Endometriosis can lead to both localized
and generalized abdominal pain as well as functional disorders of pelvic organs. In addition,
inflammation of any pelvic viscera or peritoneum can generate a response in other organs and
muscles that produce increased muscle spasms or other functional disorders such as
dysmenorrhea, bladder overactivity, and symptoms of irritable bowel syndrome (104). This
overlap in symptoms often results in diagnostic delay of several years and can lead to
significant psychological distress in patients experiencing pain from endometriosis (Figure 1).
Although, women with endometriosis experience significantly more lower abdominal pain,
dysmenorrhea, or menorrhagia in compared to matched controls without endometriosis,
women without demonstrable endometriosis may also experience pelvic pain (9) which may
also confuse the clinical picture.
Pelvic pain from endometriosis may be as a result of inflammation and cytokines
produced by endometrial implants (117; 125). The site and depth of infiltrating implants often
correlate with bowel pain (8) and lower urinary tract dysfunction and pain. Bowel or urinary
pelvic pain in women with endometriosis may be temporarily exacerbated during menses
(13).
Due to the complex nature of endometriosis, establishing a validated research model of
the disease is crucial to identifying underlying mechanisms and developing novel therapeutic
targets. Although none of the currently available animal models succeeds completely in
mimicking all aspects of human disease, they have proven valuable tools for the design of
controlled experiments (115). The most commonly used models for endometriosis research
have been established using either non-human primates or rodent strains. Because of the
expense and ethics associated with the use of non-human primate models, rodent models have
been of larger use. In rodent models endometriosis can be induced surgically by auto-
transplanting portions of the uterine horn onto mesentery proper (47; 121) or by peritoneal
injection of endometrial tissue (32). Upon surgical induction, the uterine transplants develop
into cysts with characteristics similar to ectopic endometrial growths in women with
endometriosis (105). In rats with experimentally induced endometriosis, the cysts disappear
after ovariectomy and reappear after estradiol replacement. These animals also exhibit vaginal
and abdominal muscle hyperalgesia with severity that varies with estrous cycle and plasma
estradiol levels (22; 74). The endometriosis induced vaginal hyperalgesia in rats is mainly
centrally-mediated because the abdominal cysts develop a nerve supply that sends afferents to
mid-thoracic spinal segments and the brainstem via splanchnic and vagus nerves, respectively
(22), and spinal cord transaction eliminates vaginal hyperalgesia (74). Berkley et al. (2007)
demonstrated that endometriosis-induced vaginal hyperalgesia is exacerbated by estradiol
only in rats that did not previously experience a loss in estradiol as, for example, in
ovariectomy (12). Additional basic and translational studies are warranted to clarify the
pathopysiological mechanisms of pain in endometriosis.
1.2. Vulvodynia
Vulvodynia is defined as chronic vulvar burning, stinging, or pain in the absence of clear
pathology (30). The XVII World Congress of the International Society for the Study of
Vulvovaginal Disease (2003) defined vulvodynia as vulvar pain in the absence of visible
lesions or a clinically identifiable structural changes. The prevalence of this syndrome has
been reported to be 3-16% in women (7; 44; 96). The etiology, diagnosis, and optimal
clinical management of this disorder are still unclear. Vulvodynia is characterized by
generalized or provoked vulvar pain of varying intensity without obvious clinical pathology.
Vulvar vestibulitis syndrome (VVS) is a combination of symptoms and findings limited to the
vulvar vestibule that consists of 1) severe pain on vestibular touch to attempted vaginal entry,
2) tenderness to pressure localized within the vulvar vestibule, and 3) physical findings
confined to vulvar erythema of various degrees (134).
The pathogenesis of vulvodynia is not well understood. It has been attributed to changes
in estrogen concentration, embryologic abnormalities, increased urinary oxalates, and
immune factors. Studies suggest that estrogen affects sensory discrimination and pain
sensitivity at multiple sites within the central and peripheral nervous systems and, possibly,
alter innervation of estrogen responsive targets (138). Fluctuations in estrogen concentration
correlate with vulvar nerve density and processing of sensory inputs. This may explain why
vulvodynia often occurs at the onset of menopause (7).
A number of conditions have been associated with pelvic floor dysfunction and
accompanied by vulvar pain. Anxiety and history of sexual abuse was shown to be associated
with significant vulvar pain (89). Primary or secondary pelvic floor muscle dysfunction in
women was also linked to chronic vulvar pain (39). For instance, traumatic vaginal delivery
can result in neuromuscular injury to the pelvic floor leading to pelvic floor muscle spasm
and pain (95). Additionally, vulvodynia has been associated with vaginal yeast infections (6;
7).
Pathologic findings in women with vulvodynia include chronic inflammation, increased
peripheral innervations and tonic contraction of the levator ani muscle (78). In a study by
Foster et al. (1997), vulvar tissue samples showed an increase in the median tissue levels of
IL-1b and TNF- of 2.3 and 1.8 fold, respectively, in women with VVS compared to controls
(34). In another study of vulvar tissue histology, total inflammatory infiltrate, number of mast
cells, and total nerve fiber density were significantly higher in VVS patients compared to
normal controls (16). Tympanidis et al. (2003) observed a significant increase in
immunostaining for the neuronal marker protein gene product 9.5 (PGP 9.5) but not for the
calitonin gene-related peptide (CGRP) in 12 vulvar biopsies from women with vulvodynia
compared to 8 biopsies from normal controls (118). The absence of appropriate animal
models for the studies of vulvodynia significantly delays the identification of the neural
pathways and mediators of vulvodynia associated pain.
1.3. Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) in Women
Interstitial cystitis/Painful bladder syndrome (IC/PBS) is a debilitating medical condition

characterized by chronic pelvic pain, urinary urgency, frequency and possibly nocturia in the
absence of any identifiable pathology (21; 84). One third of women with CPP may have
IC/PBS and 85% of women with CPP have pain of bladder origin (84). The clinical
presentation of IC/PBS is similar to that of many other conditions commonly seen in female
patients, including recurrent urinary tract infections, endometriosis, chronic pelvic pain,
vulvodynia, and overactive bladder (29). In a study of 162 women with CPP who underwent
both cystoscopy with hydrodistension and diagnostic laparoscopy, 76% were diagnosed with
active endometriosis, 82% with IC/PBS and 66% had both entities (86). The results from
another group showed that 38% of women scheduled for laparoscopy for suspected
endometriosis were cystoscopically confirmed to have IC/PBS (24).
The majority of patients with painful bladder disorders and idiopathic sensory urgency
are women (66) and 90% of IC/PBS patients are females (2). Pain and symptoms of IC/PBS
have been shown to fluctuate during the menstrual cycle. Most symptoms were reported to
worsen during the late luteal and early follicular phases of the menstrual cycle along with
pain thresholds in women with CPP (71). As many as 40% of IC/PBS patients indicate that
symptoms worsen perimenstrually, and often improve during pregnancy (128). Two thirds of
226 women with IC/PBS experience pain at multiple sites including suprapubic, urethral,
genital and nongenitourinary pain (126). Using psychophysical methods to compare the effect
of the menstrual cycle on bladder sensation in women with the diagnosis of IC/PBS to
controls, Powell-Boone T et al. (2005) found that subjects with IC/PBS had higher pain
scores and urinary frequency throughout the menstrual cycle compared to controls (92).
Interestingly, the highest pain scores were noted in the perimenstrual period while lower
cystometric volumes were needed to evoke bladder pain in the follicular phase of the
menstrual cycle in women with IC/PBS (92). This suggests that the normal fluctuations in
ovarian hormones are, in part, contributors to the sensory aspect of pain in premenopausal
women.
Detailed analysis of clinical data suggests that the bladder is not always the pain
generator in IC/PBS. It is possible that peripheral neurogenic inflammation together with
central sensitization play a role in the generation and maintenance of IC/PBS symptoms,
especially, urinary urgency and frequency (75). Enhanced sensitivity may be present in the
bladder itself, or may be due to increased activity within the central nervous system.
Alterations in neural pathways may underlie the tenderness that is present in IC/PBS patients
(63). It is possible that an increase in visceral (bladder) sensitivity may be secondary to a
primary somatic injury that sensitized central pathways.
Many studies have documented that patients with IC/PBS have urothelial abnormalities
present in bladder biopsies. These abnormalities included altered bladder epithelial expression
of HLA Class I and II antigens; decreased expression of uroplakin and chondroitin sulfate;
altered cytokeratin profile, and changed integrity of the glycosaminoglycan layer (20; 31; 38;
50; 107). The glycosaminoglycan layer normally coats the urothelial surface and renders it
impermeable to solutes. Abnormalities in the urothelial lining may increase the permeability
allowing for the passage of noxious toxins from urine to irritate the submucosal layer. (83).
Chronic irritation by toxins may induce further tissue damage, pain, and hypersensitivity.
Bladder mast cells may also play a role in the propagation of ongoing bladder damage after an
initial insult (114). In addition, the expression of IL-6 and P2X3 ATP receptors is increased in
bladder biopsies from women with IC/PBS compared to controls (56; 79). Importantly, it is
not known whether these urothelial abnormalities represent the primary etiology of IC/PBS or
they are secondary to the clinical syndrome.
1.4. Clinical Correlations between Hormonal Fluctuations and

Genitourinary Pain
Sex steroid hormones play a key role in pain perception in female patients. Results of
clinical research provide evidence that a womans menstrual cycle influences her perception
of experimentally induced pain (99). Giamberardino et al. (1997) examined pain thresholds to
electrical stimulation in parietal tissues as a function of menstrual cycle and found that pain
thresholds are lower during the periovulatory stage (37). Another study by Fillingim et al.
(1997) documented menstrual phase by urinary and plasma hormones using a repeated
measures design (33). They found statistically significant differences in the threshold for
ischemic pain with higher tolerances during the follicular phase in comparison with ovulatory
and luteal phases. This study also determined a correlation between higher estrogen levels and
increased thermal pain sensitivity (33). Pfleeger et al. documented that among 11 normally
menstruating women pain tolerance and threshold times were significantly longer in the
follicular phase compared to the luteal phase (91). In 24 healthy volunteers, the thermal cold
perception threshold at the mammilla was significantly lower in the late follicular and mid-
luteal phases compared with the early follicular phase (108). A meta-analysis of 16 published
studies, examining the associations between the perception of experimentally induced pain
across menstrual cycle phases in healthy women demonstrated that for pressure induced pain,
thermal stimulation, or ischemic muscle pain, healthy menstruating women demonstrated less
pain sensitivity during the follicular phase while, for electrical stimulation, the luteal phase
was the least sensitive (99). However, the menstrual cycle did not seem to influence the
affective modulation of pain and nociception in healthy women in a recent study by Rhudy et
al. (98).
In addition to the effects of the menstrual cycle on the perception of pain in healthy
individuals, sex hormones have been implicated in pain sensitivity among women diagnosed
with a prior pain disorder. Normally menstruating women with a history of fibromyalga were
noted to have significantly higher mid-luteal progesterone levels and experience more pain
compared to normally menstruating controls (76). Other studies demonstrated an increase in
gastrointestinal symptoms including bowel discomfort, abdominal pain and bloating, and
alterations in bowel patterns in women with and without irritable bowel syndrome (IBS) at
times of declining or low ovarian hormones linking bowel pain to estrogen or progesterone
withdrawal (45). These studies suggest a strong physiologic role of ovarian hormones in pain
perception and processing in women.
2. Basic Mechanisms Underlying

Genitourinary Pain
The prevalence of genitourinary pain in women points toward possible involvement of
ovarian hormones in modulation of neurogenic inflammation in the pelvis through interaction
with a variety of mediators of pain and inflammation (102). Recent articles provide evidence
that the co-occurrence of urinary, reproductive and non-specific pain symptoms may be due
to the development of neurogenic inflammation and cross-sensitization in the pelvis via
neural mechanisms (69) and on the possible modulation of such pain by sex hormones (25).
2.1. Innervation of the Pelvic Organs in Females
The female pelvis contains layers of connective tissue, muscle, and pelvic viscera
(organs). The pelvic viscera include the urethra, bladder, vagina, rectum, uterus, fallopian
tubes and the distal gut (127). With the exception of fallopian tubes, the pelvic viscera are
attached to the pelvic sidewalls by a combination of connective tissue and smooth muscle that
form ligaments and endopelvic fascia (28). The levator ani muscle complex underlies the
pelvic viscera and is comprised of the puborectalis, the pubococcygeus, and the iliococcygeus
muscles.
The function of the pelvic organs is controlled by both the central (CNS) and autonomic
nervous systems. The autonomic nerves, including the paravertebral and prevertebral
ganglionic chains, coordinate the activities of the visceral organs and sensations generated
from them (58). Prevertebral ganglia (e.g., inferior mesenteric and major pelvic ganglia)
typically consist of a mixture of cell bodies of sympathetic and parasympathetic
postganglionic neurons, receiving both sympathetic and parasympathetic input (35).
Sympathetic innervations to the pelvic viscera arise from the lower thoracic and upper lumbar
ganglia and include mainly hypogastric and lumbar splanchnic nerves whereas
parasympathetic branch is presented mostly by pelvic and pudendal nerves. The pudendal
nerve originates from the sacral segments and its branches supply the majority of both motor
and sensory fibers to the skin of the anus, clitoris, and medial and inferior vulva.
Structurally, it is not possible to distinguish afferent fibers convening sensory information
from the pelvic organs to the CNS into morphologically independent tracts. The majority of
both sensory and motor fibers accompanies the vascular system from the organ and then
enters plexuses of the autonomic nervous system before entering white rami. Sensory dorsal
root ganglion (DRG) neurons are pseudounipolar cells having a long axon which
dichotomizes into long branch projecting to the periphery and the shorter one projecting to the
spinal cord. In the spinal cord, central endings of DRG axon terminate on second-order
neurons leading to conscious perception of visceral events, as well as to activation of efferent
pathways back to the pelvic viscera (4). Interestingly, autonomic ganglia have peptidergic
varicosities which are derived from passing afferent fibers projecting towards their
corresponding target organs (48; 54).
Sensory information is mainly transmitted via afferent fibers consisting of lightly
myelinated A- and unmyelinated C fibers upon noxious stimulation of the pelvic viscera.
The A- fibers transmit noxious stimuli with high intensity and short latency. They are
generally mechanosensitive but have been shown to undergo phenotypic changes in response
to noxious stimuli (42). C fibers transmit painful sensations more slowly than A- fibers and
respond to thermo-, mechano- or chemosensitive stimulation (43; 72). The responses of A-
and C fibers are tissue and stimulus specific. For example, normal bladder filling can activate
the A- fibers while C-fibers are silent until activated by noxious irritation (42). However, in
striated muscle, activation of A- and C-fibers may similarly occur via mechanical, thermal,
and chemical stimuli (129). Both myelinated and unmyelinated afferent fibers may undergo
phenotypic changes in response to noxious or chronic stimuli.
2.2. Basic Mechanisms Underlying Multisystemic Pain Syndromes
Several neural pathways are suggested to be involved in the occurrence and distribution
of genitourinary pain including alterations in prespinal, spinal and supraspinal processing (11;
69). Viscerovisceral pathologic interactions and reflexes between the urinary and
reproductive systems are mediated by convergence of sensory information via both the
peripheral and central mechanisms of afferent stimulus processing (19). Major peripheral
mechanisms involve the afferent fibers and primary sensory neurons localized within dorsal
root ganglia (DRG), whereas central mechanisms include regions in the spinal cord and brain
(69).
Three interconnected neural pathways underlie the development of pelvic organ cross-
sensitization. The first pathway includes propagation of a noxious stimulus from a diseased
organ to a neuronal cell body within the respective DRG, often resulting in its altered
excitability (14; 133). If the same neuron has an axonal connection with an adjacent pelvic
structure, antidromic action potential propagation due to an axon-reflex mechanism may
trigger the release of neurotransmitters and peptides at the site of that organ. This, in turn,
may cause vasodilation and/or extravasation in the secondary viscus and eventually lead to
the development of neurogenic inflammation in the latter (5; 127; 131). This pathway
considers the presence of DRG cell bodies with branching or multiple axons which could
serve as direct neuronal connections between pelvic organs (70). The second pathway of
noxious stimulus transmission from one pelvic organ to another incorporates the level of the
spinal cord. Afferent input from a diseased structure and from a normal domain may converge
on the same spinal interneuron located in the dorsal horn of the spinal cord (94). The third
pathway underlying pelvic organ cross-sensitization appears to involve higher centers of the
brain. Descending feedback from the brain in response to visceral hyperalgesia and irritation
of the pelvic organs might have a huge impact on the persistence and distribution of CPP.
Stress and anxiety as a result of CPP play a significant role in the modulation of this pathway
(17).
Basic science studies implying rodent models of acute and chronic inflammation in the
pelvis clarified the conditions under which cross-sensitization in the pelvis develops as well
as some of the underlying mechanisms. A model of neural crosstalk and irritation in the pelvis
(90) revealed that acute cystitis lowers distal colonic sensory thresholds to colorectal
distension, and that acute intracolonic irritation with trinitrobenzene sulfonic acid (TNBS)
leads to the development of a neurogenic bladder. Another study from the same group has
shown that 60% of sensory endings in the bladder have increased baseline firing rate after
TNBS-induced colitis (120). The fact that urinary bladder denervation significantly abolishes
the increased firing rate of bladder afferents induced by experimental colitis suggests that
colonic inflammation modulates the sensitivity of afferent endings in the bladder by a
neurogenic mechanism (119). Experiments with TNBS-induced colonic inflammation in mice
also showed considerable urinary bladder overactivity demonstrated by more frequent
micturition with colitis, in addition to substantial visceral and somatic hypersensitivity (15).
Cross-organ sensitization caused by the uterine capsaicin instillation in the rats increased
significantly during the proestrus stage when compared with the metestrus suggesting that
estrogens might modulate cross-organ sensitization between the uterus and the urethra (88).
Mechanisms of estradiol action may also include activation of the phosphatidylinositol-3-
kinase cascade in the spinal cord to facilitate NMDA-dependent cross-organ sensitization
among reproductive and urinary organs (87).
2.3. Modulation of Neurogenic Inflammation and Cross-Sensitization in the

Pelvis by Ovarian Hormones.
Steroidal hormones have the capacity to modulate neurogenic inflammation through

interaction with a variety of inflammatory and pain mediators. Estrogen - (ER) and
(ER)-receptors are widely expressed in the nervous system including DRG (111), the spinal
cord (3), the basal forebrain, the hippocampus, and other brain regions (106). Clinical studies
determined that estrogen deficiency in women, especially long-term, is associated with a wide
range of urogenital complaints, including frequency, nocturia, incontinence, urinary tract
infections and urgency (46). Some animal data suggest that the pro-nociceptive effects of
estrogen may be due to a mismatch between peripheral and central effects of the hormones
which occur during rapidly decreasing estrogen levels (100). Estrogens have not been
extensively investigated in the peripheral nervous system, although ER expression has been
reported in sensory and autonomic ganglia innervating the urogenital organs (10; 82; 85;
109). Estradiol can regulate the expression of many neuropeptides and proteins in DRG,
including preprotachykinin (65), calcitonin gene-related peptide (CGRP); (36), and nerve
growth factor (NGF) receptors (59). Likewise, estrogens may influence a variety of peripheral
neuronal functions via ER-mediated mechanisms (93).
Although it is unlikely that fluctuations in plasma estrogen concentrations alone stimulate
pain and inflammation, estrogen may play a role in determining the onset, intensity or
duration of the response to neurogenic inflammation within the bladder. Dorsal root ganglion
neurons express both ER- and ER- receptors localized mainly in neuronal cell nuclei (10;
81; 85). Both ER and ER mRNA levels in the DRG from intact cycling female rats were
higher during proestrus compared to metestrus (111). It has been shown that low
concentrations of 17-estradiol, which acts via ER- receptors, increased survival of cultured
DRG neurons deprived of NGF (85). Xu et al (132) determined that 17-estradiol acts directly
on DRG neurons to reduce transient potential vanilloid 1 (TRPV1) receptor activation by
capsaicin. TRPV1 in DRG sensory neurons can be inhibited by a non-classical estrogen-
signaling pathway that is downstream of intracellular ER-. The results of this study are
consistent with clinical reports that female pelvic pain can increase following reductions in
circulating estrogens (71). ER- and ER- stimulate different signaling pathways and,
therefore, may differentially influence the extent and direction of neurotrophin expression
(52). Estrogen and neurotrophins also influence each other's actions by regulating receptor
and ligand availability or by reciprocal regulation at the level of signal transduction or gene
transcription. They also can stimulate the synthesis of proteins required for neuronal
differentiation, survival and maintenance of function (116).
Bladder mast cells were shown to express high-affinity estrogen receptors with high
numbers of these cells in female patients with IC/PBS (80). It was demonstrated that estradiol
augments histamine secretion in mast cells in response to SP (40; 61) and also enhances in
vitro carbachol- or substance P induced mast cell degranulation, (110; 123) and progesterone-
stimulated serotonin secretion by isolated rat peritoneal mast cells (124). Release of histamine
from mast cells can cause vasodilation and, as a result, the development of neurogenic
inflammation in the pelvis (131). In a model of a neurogenic cystitis associated with bladder
lamina propria mast cell accumulation and pelvic pain caused by pseudorabies virus (PRV)
infection in mice, significant reduction of PRV-induced pelvic pain was observed for animals
treated with antagonists of neurokinin receptor 1 (NK1R) and histamine receptors (101).
Increased NGF was observed in the urothelium of biopsies obtained from women with
painful bladder symptoms (66), while increased NGF, neurotrophin-3, and glial cell line
derived neurotrophic factor were found in urine from IC/PBS patients (77). Lamb et al (57)
examined the effect of NGF on the urinary bladder function using viral gene transfer in vivo.
Expression of NGF led to bladder overactivity, whereas -galactosidase expression had no
effect. NGF also reduced the threshold of peripheral nerves to stimulation (68) and directly
influenced the function of afferent fibers (62). Chronic systemic treatment of adult rats with
NGF enhanced innervation of the urogenital tract in comparison to the cardiovascular system,
confirming that NGF role in the urogenital tract may be somewhat unique in its capacity for
continued plasticity of innervation (73). This is particularly intriguing in light of reports of
increased density of innervation in bladder biopsies obtained from IC/PBS patients (23; 67;
80). Although altered NGF synthesis and release in response to estrogen may not directly
stimulate pain, estrogen can indirectly render the bladder more sensitive to the effects of
noxious stimuli.
2.4. Effects of Estrogens on the Urinary Bladder Function: Animal Studies
Both estrogen receptors ER- and ER- have been detected within the bladder mucosa by
immunohistochemistry, and ER- is the predominant isoform expressed in the basal cell layer
of the urothelium (103; 112). About a third of the bladder-projecting neurons expressed both
ER and TRPV1, suggesting a mechanism by which estrogens could influence bladder pain.
The coexistence of ER- and ER- suggests a broad range of potential mechanisms by which
estrogens may exert their genomic effects in this system (10). Experiments in female rabbits
showed that ovariectomy results in significantly decreased bladder contractile function
followed by an increase in the ER density (64). Chemically induced cystitis reduces the ER
expression levels in the urinary bladders of rats and is more severe in ovariectomized animals
(113). Estrogen also has been implicated in the etiology of IC/PBS. Recent studies
determined that EB-deficient female mice develop a bladder phenotype resembling human
IC/PBS (51). In this study bladders of male ER/ mice were intact and morphologically
indistinguishable from those of their wild type littermates. However, in female ER/ mice,
there was ulceration and atrophy of bladder urothelium concomitant with infiltration of T
cells concentrated in the areas of atrophy and shedding of urothelium. These results suggest
that in female ER/ (but not in ER/ ) mice there is autoimmune destruction of
urothelium resembling IC/PBS.
Increasing evidence from animal studies indicates that under normal physiological
conditions the effects of ovarian hormones on the function of different pelvic structures are
quite minimal, but become more prominent upon pathological changes in one of the pelvic
organs. For example, no estrous influences on the micturition threshold in non-inflamed
bladder were determined in rats, however, bladder inflammation substantially lowered the
micturition threshold in proestrus and estrus (53). Multi- and single-unit recordings from
gracile nucleus in rats have demonstrated cycle-dependent changes of neuronal activity in
response to tactile stimulation of the skin in the pelvic region and/or of reproductive organs,
but not the colon (18). Experiments with extravasation of Evans Blue dye in rats revealed
increased vascular permeability in the intact urinary bladder in proestrus after either colonic
or uterine inflammation. However, these changes were insignificant in metestrus (130).
Conclusions and Perspectives

Genitourinary pain is a complex and multifactorial clinical entity and maybe a symptom
of a systemic pelvic floor disorder in women (55). Improved treatments of genitourinary
pain require a thorough understanding of the processes and mechanisms underlying the
occurrence and transmission of painful stimuli in the pelvis. The leading theory for
persistent genitourinary pain in the absence of noxious stimuli is the presence of central and
peripheral sensitization following an initial insult. Pathophysiologic mechanisms are linked to
the unique hormonal milieu specific to women (either premenopausal or postmenopausal) and
must be considered in order to optimize therapeutic approaches for women suffering from
persistent genitourinary pain. Additional studies are needed to clarify sex specific
differences in genitourinary pain; determine genetic mechanisms and predisposition for the
development of pelvic pain syndromes; identify the molecules and neuronal pathways
involved in nociception/pain perception and affective aspects of pain; address
experimentally the relationship between pain of neurogenic origin, gonadal steroids and
cyclic hormonal fluctuations using screening for pain biomarkers in women with
genitourinary pain. Assessment of different profiles of pain quality, spatial characteristics
and pain patterns in response to ovarian hormone fluctuations would contribute to
identification of distinct pathophysiolgical mechanisms of genitourinary pain and lead to the
development of mechanism-based treatment approaches that can be used to alleviate pelvic
pain in women. Multidimensional and multifactorial nature of genitourinary pain should be
taken into consideration in order to develop therapeutic methods and interventions to
manage co-morbid conditions of pelvic pain syndromes.
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Chapter V
Pathophysiology of Endometriosis-
Associated Pelvic Pain
Julia Arnold and Sylvia Mechsner*

Endometriosis Research Centre Charit, Department of Gynaecology,
Campus Benjamin Franklin, Berlin, Germany
Abstract
Endometriosis is an estrogen-dependent disease, characterised by the presence of
endometrial glands, stromal and smooth muscle cells outside the uterine cavity, affecting
10-15% of women in reproductive age. The gold standart to diagnose endometriosis is
visualization at surgery.The average diagnostic effort takes up to 8 years.
50 to 60% of women and teenage girls with pelvic pain suffer from endometriosis
while other symptoms like severe dysmenorrhea, chronic pelvic pain, dyspareunia,
dyschezia and dysuria often occure coevally. Endometriosis causes disability and
compromised quality of life in women and young girls.
Pain generation in endometriosis is an intricate interplay of several factors such as
the endometriotic lesions itself and the pain mediating substances produced there, nerve
fibers and cytokine releasing immune cells and macrophages. These interactions seem to
induce a neurogenic inflammatory process.
The detection of nerve fibers in eutopic endometrium and in ectopic endometriotic
lesions of patients with endometriosis suggests that the pain sensation is due to the
neurotrophic properties of endometriosis. Recently, NGF (nerve growth factor), a pain
mediator and important nerve growth factor, was found in the peritoneal fluid of patients
with endometriosis, leading to a significantly increased neurite outgrowth from sensory
ganglia compared with the peritoneal fluid from patients with other benign
gynaecological diseases.
Contrary to these data, the presence of nerve fibers in endometrium of patients with
other painfully disorders like fibroids and salpingitis could be demonstrated, suggesting a
*
PD Dr. med. Sylvia Mechsner, MD, PhD, Endometriosis Research Centre Charit, Department of Gynaecology,
Charit, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany, Fax: +49 30 8445 4477,
E-mail: sylvia.mechsner@charite.de).
132 Julia Arnold and Sylvia Mechsner
pain mediator-dependent innervation, independent from the manifestation of

endometriosis.
However, the nerve fiber invasion in endometriotic tissue may be a possible
explanation for pain generation in endometriosis. Current studies of women and animal
models are beginning to give clues.
1. Introduction
1.1. Endometriosis-Associated Pain
Endometriosis is a disease affecting women of reproductive age whose symptoms,

dysmenorrhea, dyspareunia, dyschezia, dysuria, cyclic and acyclic pelvic pain, menstrual
disorders and infertility, have extreme human, clinical and economic relevance (Cramer, et al.
2002, Gao, et al. 2006).
The prevalence of endometriosis is indicated with 10-20% of all women in the above age
(Olive, et al. 2001, Goldman, et al. 1990), and therefore, represents one of the most frequent
benign gynecological diseases. Highly problematic is that the time interval from the onset of
the symptoms to the diagnosis is 6-8 years in average. This problem is due to the lack of
knowledge about the pathogenesis of endometriosis and the mechanisms of pain generation.
The often "inconspicuous" physical examinations complicate the diagnosis. Therefore, the
detailed anamnesis is often decisive, but time-consuming. To assess the full extent of the
complaints even sensitive questions about sexuality as well as fundamental questions about
family planning have to be asked.
Since a large part of affected patients complain about pain, significantly limiting their
quality of life (Sepulcri Rde, et al. 2009), a peculiar knowledge in this field is of main
importance for the diagnosis and therapy. The origin of endometriosis associated pain is still
misunderstood. The symptoms are complex and they can occur in isolation or in combination,
and they seem to have multifactorial cause. A pain profile shows that 84% of the patients
indicate both pelvic pain and dysmenorrhea; 72% indicate an additional symptom (like
dyspareunia, dysuria or dyschezie). Over 70% of the patients are affected with dyspareunia
and up to 50% with dyschezia (Mechsner, et al. 2009). The different pains of endometriosis
might be due to the different manifestations of endometriosis.
1.2. Definition and Classification of Endometriosis
Endometriosis is the presence of endometrial-like tissue outside the uterine cavity.

Endometriosis can be categorized by the various localizations. The endometriosis genitalis
externa describes the presence of endometriotic lesions on the peritoneal clousure (visceral
and parietal peritoneum) of the female internal reproductive organs (peritoneum of the uterus,
tubes and ovaries, but also of the urinary bladder, the fossa ovarica, the pouch of douglas, the
ligaments and the pelvic wall) as well as the occurrence of endometriotic ovarian cysts
(endometriomas). The endometriosis genitalis externa is classified by the American Society
for Reproductive Medicine into four stages (rASRM I-IV) (rASRM 1997), where both the
dimension of the endometriotic lesions and the formation of adhesions are considered.
Pathophysiology of Endometriosis-Associated Pelvic Pain 133
Furthermore, the endometriosis genitalis interna is defined as the occurrence of epithelial and
stromal cells in the myometrium, also called adenomyosis, and within the tubes.
Endometriosis extragenitalis is the presence of endometriotic lesions outside the female
internal reproductive organs (in the bladder, bowel, diaphragm, abdominal wall, or even
lung). Endometriotic lesions grow superficial and / or deep infiltrating with destruction of
adjacent tissues like the bowel, bladder and ureter. The rectovaginal endometriosis constitutes
a special form; it is typically located in the rectovaginal septum and the most common form
of deep infiltrating endometriosis. It is classified by the ENZIAN score (Tuttlies, et al. 2005).
This classification considers the infiltration of endometriotic tissue into adjacent organs or
anatomical structures like the sacrouterine ligaments, the vagina, ureter or bowel wall. The
organ destruction can lead to severe pain and functional disorders and in the case of the
intestinal wall to the point of a stenosis. The ectopic endometrium-like tissue causes a local
chronic inflammatory reaction, which promotes the formation of adhesions, leading to a
progression of the disease and to other secondary changes of the internal genitalia with the
appropriate functional impairment.
Because of that, endometriosis is often associated with complex symptoms, although the
severity of pain and the stage of disease (rASRM) are out of proportion (Gruppo italioano per
lo studio 2001, Fedele, et al. 1992, Vercellini, et al. 1996). Conclusions can indeed be drawn
concerning the nature of pain following the manifestation of endometriosis (Koninckx, et al.
1991, Fauconnier, et al. 2002, Fauconnier, et al. 2005) but the symptoms of various
manifestations overlap as well. Patients with adenomyosis for example usually have
dysmenorrhea, but might also suffer from cyclical pelvic pain (Parker, et al. 2006). But these
symptoms may also be present when endometriosis genitalis externa is solely present. All
manifestations of endometriosis may lead to dysmenorrhoea, despite of that microbleedings in
the lesions also play a role (Brosens et al., 1997, Vercellini et al., 1997). Dyspareunia may be
present in adenomyosis uteri, endometriosis genitalis externa, and particularly in patients with
rectovaginal endometriosis. In contrast, dyschezia or dysuria suggests an involvement of the
bladder or the bowel (Table 1).
Table 1
Symptoms Localisation
Dysmenorrhoea Adenomyosis
Peritoneal lesions
Deep infiltrating Endometriosis
Pelvic pain peritoneal and ovarian lesions
Adhesions
Adenomyosis
Dyspareunia Rectovaginal Endometriosis, lesions of the douglas
and sacrouterine ligaments
Dyschezia/Dysuria Gut and bladder involvement
Hmatochezia/Hmatouria
Infertility Adenomyosis/Endometriosis
Endometriomas
Adhesions
Closure of the tubes
2. Pathophysiology of Endometriosis-Associated
Pain
2.1. Complexity of Endometriosis-Associated Pain
To understand endometriosis-related pain is very difficult, especially the different forms

of pain (pelvic pain, dysmenorrhoea, dysuria und dyschezia), exacerbated, the character of the
pain is determined by the localization of the lesions.
Therefore, depending on the manifestation of endometriosis both somatic and visceral
pain can be present. Somatic pain emanating from the pelvic wall, muscles or joints can often
be localized well and tend to be described as sharp or pointed. Visceral pain originates from
intraperitoneal organs, which are supplied by sympathetic innervation. This pain is often
poorly locatable and is described as dull and cramping and may spread over several
dermatomes. It is often also associated with nausea and emesis. Furthermore, there is a
complex interaction between the reproductive organs, the urogenital tract and the intestine, so
that its differentiation is often hard, especially when the pain becomes chronical (Vercellini,
et al. 2009). Further complications arise when adhesion-related pain joins, often characterized
by a transition of cyclic to acyclic pelvic pain.
Due to the chonic pain, patients often develop a reactive depression over the time and
also somatoform pain disorders, because of the chronic pain situation, which makes the
disease even more complex. The main differential diagnoses of chronic pelvic pain despite of
endometriosis are: post-operative adhesions (not endometriosis-related), pelvic inflammatory
diseases (PID), pelvine varikosis, interstitial cystitis and non-specific intestinal disorders, like
the irritable bowel syndrome or previous physical and/or sexual abuse.
However, the evaluation of pelvic pain is difficult since the characteristics of this pain are
often hard to describe or localize accurately for women. This is probably due to the fact that
there is a reduced concentration of sensory ganglia in the pelvis than in the conjunctiva of the
skin or the periosteum of the bone. As a result it is difficult for the pain-perceiving centers in
the brain to make a sharp differentiation as to the location, type and severity of the pain. This
is also the primary reason that ovarian carcinoma has such a poor prognosis. It causes no
discomfort in the early stages, even though the tumor has grown to a large size. In contrast,
great discomfort can be caused by small implants of endometriosis (Long 1990).
2.2. What is Pelvic Pain?
Pelvic pain is an abdominal pain located below the level of the umbilicus. This pain can
be acute or chronically.
A delimited form of pelvic pain is the chronic cyclical pelvic pain (CCPP), which occurs
within the menstrual cycle and is due to hormonal causes. It often occurs during menstruation.
However, CCPP also includes pelvic pain occurring in a cyclic pattern, but not related to the
menstrual bleeding for example during ovulation; the so called "Mittelschmerz (German for
middle pain) (Won, et al. 2010). Furthermore, pelvic pain may also follow no cyclical
pattern and is therefore not related to hormonal fluctuations (ACOG Practice Bulletin No. 51
2004).
Further delimited forms of pelvic pain are dyspareunia and dysmenorrhea. Dyspareunia is
pelvic pain associated with intercourse. And dysmenorrhea is defined as a painful
menstruation and can be classified as either primary or secondary, based on the absence or
presence of an underlying cause. A painful menstruation without pelvic pathologies is called a
primary dysmenorrhea, whereas secondary dysmenorrhea is associated with an existing
condition like endometriosis (French 2008).
Following, the pathophysiological aspects of dysmenorrhoea, pelvic pain and
dyspareunia will be explained in more detail.
2.2.1. Dysmenorrhea
Dysmenorrhea is described as an intermittent cramping discomfort in the lower abdomen
and pelvis. It may also be associated with a bearing-down sensation, backache, and epigastria
discomfort and nausea/emesis. Seizures in the legs are also not uncommon. A syndrome of
premenstrual tension often precedes the appearance of menstrual flow. This syndrome may
often include headache, obstipation, fluid retention, weight gain, flatulence, mild depression
and abdominal tenderness.
Although dysmenorrhea reflects a great social and economic problem of patients with
endometriosis and adenomyosis (Akerlund 1976 (Gao, et al. 2006), there is still very little
known about the pathophysiology of adenomyosis and endometriosis-associated
dysmenorrhea.
2.2.1.1. Primary Dysmenorrhea

Myometrial hyperactivity and reduced uterine blood flow which causes ischemic pain is a
well-established phenomenon in women with primary dysmenorrhea (Akerlund, et al. 1976).
Possible etiological factors of primary dysmenorrhea and their mechanism of action are
substances leading to myometrial contractility, such as oxytocin (OT), vasopressin (VP) and
prostaglandin (PG) F2 (Liedman, et al. 2008). Both VP and OT plasma levels are increased
in women with dysmenorrhea (Akerlund 1993, Akerlund, et al. 1979, Ekstrom, et al. 1992,
Stromberg, et al. 1984). Oxytocin receptor (OTR) and vasopressin receptor (VPR) have been
demonstrated to be present in the myometrium of non-pregnant women (Lee, et al. 1998,
Maggi, et al. 1992). Uterotonic peptides, for example OT, VP, endothelin, noradrenaline
and/or endoperoxins may possibly contribute to the vasoconstriction of dysmenorrhea, and
have a distinct influence on the resistance of uterine arteries. The synthesis of PGF2 takes
mainly place in the endometrium under the influence of OT, estradiol and progesterone. The
menstrual blood PGF2 concentration of women with dysmenorrhea is higher than in women
without dysmenorrhea (Lumsden, et al. 1983). PGF2 activates pain by stimulation of uterine
contractions and afferent nerve fiber activation; and therefore leading to a pain sensation
(Lerner, et al. 1985).
The role of OT and VP in primary dysmenorrhea is supported by the therapeutic effect of
the competitive OT and VP receptor antagonist (Akerlund 1987, Akerlund, et al. 1995,
Steinwall, et al. 2004, Steinwall, et al. 2004). This has been confirmed by usage of a
therapeutic treatment of dysmenorrhea with oral contraceptives, and works by reducing the
plasma levels of OT, VP and estrogen receptors (ER) (Akerlund 1993, Ekstrom, et al. 1992,
Akerlund 1987). Additional administration of ethanol, which inhibits the release of both
neurohypophysial hormones, VP and OT, results in a complete suppression of uterine
contractility in non-pregnant women (Fuchs, et al. 1971).
2.2.1.2. Endometriosis and Adenomyosis-Associated Dysmenorrhoea

A concomitancy of adenomyosis and endometriosis seems to be in more than 90% of the
cases (Kunz, et al. 2005). Most complaints of patients with adenomyosis are dysmenorrhea
(30-50%), menorrhagia (50%), metorrhagia (20%), and occasionally dyspareunia and pelvic
pain as well as infertility (Peric, et al. 2006). So that it has to be assumed that adenomyosis is
a main cause of dysmenorrhea. The frequency and severity of symptoms correlates with the
extent (Benson, et al. 1958) and depth of the adenomyotic foci in the myometrium (Nishida
1991).
2.2.1.2.1. Hyper- and Dysperitalsis

Recently, it could to be demonstrated that the uteri of patients with adenomyosis and
endometriosis show a pathological pattern of contractility similar to that seen in the
hyperperistalsis and dysperistalsis of myometrial cells (Bulletti, et al. 2002, Leyendecker, et
al. 1996). In the non-pregnant uterus, uterine contractions originate exclusively from the
junctional zone (Bulletti, et al. 2002, Brosens, et al. 1995, de Vries, et al. 1990, Lyons, et al.
1991). Furthermore the expression of the OTR and VPR could be demonstrated in patients
with adenomyosis (Mechsner, et al. 2010).
The myometrium represents at least two functionally and structurally distinct zones: the
subendometrial or junctional zone and the outer myometrium (Brosens, et al. 1995, Brosens,
et al. 1998, Brosens, et al. 1998, Daels 1974, Fujii, et al. 1989, Leyendecker, et al. 2005).
Especially the important findings of morphological changes in the architecture of the
myometrium in patients with adenomyosis are of great interest. The passage between the
junctional zone and the endometrium in patients with adenomyosis is to a significant extent
more frequently fissured than in those without adenomyosis (Mechsner, et al. 2010).
It seems possible that the hyperperistalsis described in patients with adenomyosis leads to
a disrupture of the endometrial basal layer with infiltration of endometrial cells (archimetra-
concept) (Leyendecker, et al. 2005). Kitai et al described such histomorphological changes of
an irregular passage between endometrium and myometrium in patients with adenomyosis
(Kitai 1924).
Furthermore, the adenomyosis-associated myometrium surrounding the adenomyotic
lesion was seen to be very compact compared to unaffected myometrium. It also shows an
OTR over-expression in nearly 50% of the cases investigated, as well as OTR positive intra-
stromal smooth muscle cells, suggesting that the metaplastic activity of adenomyotic cells
results in myometrial hyperplasticity/ metaplasia (Fujii, et al. 1989, Leyendecker, et al. 2005,
Kitai 1924, de Snoo 1942, Konishi, et al. 1984, Leyendecker, et al. 1998, Ferenczy 1998,
Meyer 1930). The disturbance of the architecture promotes peristalsis and leads to pain.
2.2.1.2.2. Uterine Nerve Fibers

A further point in the pathogenesis of dysmenorrhea that has to be discussed is the
presence of nerve fibers in the uterus. Some researchers have already found nerve fibers in
various uterine layers. Atwal and colleagues examined hysterectomy specimens and found a
significantly higher nerve fibers density in the endometrium of patients with pain
symptomatology (whether with or without endometriosis) compared to patients without a
painful disorder, independent from endometriosis (Atwal, et al. 2005). Coincidentally,
another group confirmed these results (Zhang, et al. 2009). In this study, the occurrence of
nerve fibers in the functional layer of the endometrium of women with fibroids or
adenomyosis with and without pain, were examined. Nerve fibers were only found in patients
with pain and the nerve fiber density increased with the severity of pain. These results
confirm the suggestion that the presence of nerve fibers in the functional layer of the
endometrium is a pain-dependent phenomenon and may pose in patients with dysmenorrhea
one of the pathogenesis factors.
In contrast, some studies demonstrated, a significant higher nerve fiber density in the
endometrium of patients with endometriosis and not in patients without endometriosis
independent from the pain severity (Tokushige, et al. 2006).
2.2.1.2.3. Deep Infiltrating Endometriosis of the Recto-Vaginal Septum

The occurrence of deep infiltrating endometriosis of the recotvaginal septum, especially
with bowel and /or vaginal infiltration, is related to the severity of dysmenorrhea. The
removal of such lesions leads to a significant decrease of dysmenorrhea (Chapron, et al.
2003).
2.2.2. Pathogenesis of Endometriosis-Associated Cyclic And

Acyclic Pelvic Pain
The pathogenesis of endometriosis-associated chronic pelvic pain is still unclear.
Peritoneal lesions, adhesions and the uterus it self are possible causes. Furthermore
chronic pelvic pain leads to a dysfunction of the pelvic floor with muscular spasm and pain
sensation.
2.2.2.1. Peritoneal Endometriotic Lesions as the Cause of Pain

The peritoneum is physiologically highly innervated; especially the parietal peritoneum
often mediates pain in diseases like acute peritonitis caused by appendicitis or a pelvic
inflammatory disease. The ovary is a relatively insensitive organ regarding to pain, which can
assume enormous proportions (for example in ovarian cancer or endometriomas) before it
causes pain, more likely due to peritoneal irritation. But why peritoneal endometriotic lesions
are resulting in such severe pain, while other peritoneal diseases like malignancies are often
completely asymptomatic, is still unknown. The possible pathogenic mechanisms of the
peritoneal endometriotic lesions include multiple factors such as the activity of the lesion
producing pain and inflammatory mediators, but also nerve fiber sprouting and possible
contractions of isolated muscle fibers in the peritoneum.
2.2.2.1.1. Inflammatory Nociceptive Pain

One explanation for the peritoneal pain is the synthesis of pain mediators by the
peritoneal lesion itself. The number of lesions, the activity and infiltration depth seem to have
an influence on the pain etiology (Chapron, et al. 2003, Vernon, et al. 1986, Vercellini 1997).
Pain mediators like prostaglandins (PG), histamine, kinins and interleukins are secreted by
peritoneal endometriotic lesions and seem to activate nociceptors (Vernon, et al. 1986, Drake,
et al. 1981, Moon, et al. 1981). Equivalent to eutopic endometrium, peritoneal lesions appear
to be under cyclical changes and therefore secrete mediators cycle-dependent (there are
unfortunately no current, adequate studies). However, there recently are some studies which
have at least demonstrated an indirectly increased PG-synthesis through an up-regulation of
COX-2 expression in peritoneal endometriosis-associated macrophages (Wu, et al. 2002) and
in ectopic endometriotic implants (Ota, et al. 2001) The COX-2 expression correlates with the
concentration of secreted PG E2 in the peritoneal fluid and with the severity of endometriosis
(Wu, et al. 2002).
This reflects the inflammatory nociceptive pain component and justifies the therapeutic
use of PG synthesis inhibitors, the non-steroidal anti-inflammatory drugs. This also explains
how often hormonal treatment (with combined oral contraceptives (COCs), progesterone-only
pill (POP) and gonadotrophin releasing hormone agonists (GnRHa), leading to the down-
regulation of the ovarian function and therefore to a halt of the cyclic activity of the lesion,
significantly improves the symptoms.
However, for a large number of patients, pain remains a part of their daily life, even after
surgical therapy or hormone treatment, a failure rate of 20-25% has been reported (Practice
Committee of American Society for Reproductive Medicine 2008). The ability to achieve a
sufficient symptom control with analgesics has hardly been studied. There are only some
studies for the treatment of dysmenorrhoea with non steroidal anti inflammatory drugs
(NSAIDs). A satisfactory pain relief could be a shown (Corson, et al. 1978, Cobellis, et al.
2004). The effectiveness of opioids on endometriosis-associated pain has also not been
studied. In gynecological practice, however, only a portion of patients with a combined
treatment of NSAIDs and opioid analgesics show a sufficient pain reduction. It also appears
that only half of the patients indicate "endometriosis-typical" or intermittent menstrual-
associated pain, while the other half complains about chronic pain (Practice Committee of
American Society for Reproductive Medicine 2008). The chronic pain often remain poorly
understood and sometimes leads to psychosomatic therapy trials under the idea that
Malcognition, negative conditioning, depressive disorders or "social stress" (after the bio-
psycho-social concept of chronic pain) may be the cause. This chronic pain is often described
as burning or stabbing; a systematic collection of endometriosis-associated pain qualities has
not yet published. As a possible cause of this pain quality, also described as neuropathic pain,
the neural invasion theory has been propagated (Practice Committee of American Society for
Reproductive Medicine 2008).
2.2.2.1.2. Neuropathic Pain

Increasingly frequent, neuropathic pain is discussed as a pathogenic mechanism in
particular when cyclic pain devolves into acyclic persistent pain. This kind of pain is often
described as burning and sharp and seems to be resistant to hormonal treatment and NSAIDs
(Vercellini, et al. 2009, Gillett, et al. 2009). It is a pain caused by the nerves itself, due to
nerve injury, infection, growing tumors and /or metabolic diseases. This leads to irritation of
the peripheral and central nervous system and therefore to a burning and stabbing pain with
paresthesia. Allodynia and hyperalgesia are other common manifestations of neuropathic
pain. Under common conditions, C-afferents terminate in the dorsal horn, where the fibers are
switched to secondary nociceptive neurons, while the A-afferents are not switched, but
projected into the dorsal columns and therefore terminate in afferent dorsal horn neurons.
Partial damaged afferent C-nociceptors either generate ectopic nerve impulses or those
nociceptors are sensitized chronically (Asante, et al. 2010). Caused by chronic sensitization
of primary afferent nociceptors, a central sensitization of the secondary afferent dorsal horn
neurons follows. This in turn activates central nociceptive neurons through A- contact-
afferents. Chronic nociceptive activity can lead to an undisturbed transmission of nociceptive
impulses, which is caused by a loss of function or degeneration of the inhibition of
nociceptive activity by noradrenaline and serotonin. The occurrence of nerve fibers in close
contact to endometriotic lesions leads to the assumption that nerve fibers were involved in
paingneration especially in development of neuropathic pain
2.2.2.1.2.1. Clinical Importance of Endometriosis-Associated Nerve Fibers

The presence of nerve fibers has been shown in ectopic endometriotic lesions like
peritoneal (Tokushige, et al. 2006, Mechsner, et al. 2007), deep infiltrating recto vaginal
(Anaf, et al. 2000) and ovarian (Zhang, et al. 2010) endometriotic lesions. If these Nerve
fibers have a clinical impact on pain generation has been investigated. It is shown that the
incidence of endometriosis-associated nerve fibers is correlated to pain intensity. The surgical
removal of peritoneal lesions showed a significant postoperative pain reduction (Kaiser, et al.
2009, Jacobson, et al. 2009).
In other manifestations of endometriosis, the nerve fiber density influences pain-related
processes. In deep infiltrating recto vaginal endometriosis, the severity of pain is directly
correlated with the number of nerve fiber findings (Anaf, et al. 2002). Furthermore, peritoneal
endometriosis-associated nerve fibers were found significantly more frequent in patients with
severe pain (Mechsner, et al. 2009), whereas the peritoneal mean nerve score of patients with
and without endometriosis remained the same. Interestingly, deeply infiltrating lesions of the
rectovaginal septum, vagina and intestine infiltrate already richly innervated tissue, but
occasionally, some lesions with enormous proportions, surprisingly, cause no symptoms.
Perhaps, these lesions associated nerve fibers are not involved in central modulation or their
transmission of the pain is limited (Vercellini 1997).
Most recently, nerve fibers could be shown in perilesional interstitium close to ovarian
endometriosis, suggesting that endometriosis-associated nerve fibers influence the
pathogenesis of pain (Zhang, et al. 2010).
2.2.2.1.2.2. Endometriosis-Associated Nerve Fibers in Peritoneal

Endometriotic Lesions
In fact, nerve fibers are in a close topographic connection with peritoneal lesions
(Tokushige, et al. 2006, Mechsner, et al. 2007). They could be characterized as sensory
myelinated A and unmyelinated C-fibers and are often accompanied by lymphocytic
infiltrates. Furthermore, these nerve fiber-colocalisations seem to appear more frequently in
peritoneal endometriotic lesions of patients with severe pain than in those with mild
symptoms (Mechsner, et al. 2009) and significantly more in patients with endometriosis
compared to those with other painful diseases, like fibroids or salpingitis (Tokushige, et al.
2006).
2.2.2.1.2.3. Neurotrophic Properties of Endometriosis

There is a number of data that clearly proves that endometriotic lesions themselves have
neurotrophic properties (Mechsner, et al. 2007, Berkley, et al. 2004, Barcena de Arellano, et
al. 2010). In a rat model of endometriosis the reinnervation of ectopic uterine slices that were
transplanted on mesenteric vessels could be seen (Berkley, et al. 2004)
Interestingly, peritoneal endometriosis-associated nerve fibers are accompanied by
immature vessels, suggesting an analogous nerve infiltration into the endometriotic lesion.
The detection of Gap-43, a marker molecule for regenerating and growing nerve fibers, in
those endometriosis-related nerve fibers reinforces this assumption. This hypothesis is
supported by the detection of nerve growth factors like nerve growth factor (NGF) and
neurotrophin-3 (NT-3) expressed by endometriotic lesions (Mechsner et al., 2007). Moreover,
neurotrophic properties of endometriosis were shown in an in vitro neuronal growth assay,
where chicken embryonic dorsal root ganglia were incubated with peritoneal fluid from
patients with and without endometriosis. The nerve fiber outgrowth of DRG, incubated with
peritoneal fluid from patients with endometriosis was significantly increased (Barcena de
Arellano, et al. 2010). In addition, a significantly higher NGF concentration in peritoneal
fluids of patients with endometriosis than without endometriosis could be discovered. The
effect of the in vitro nerve outgrowth could be blocked with NGF inhibitors, suggesting that
this is an NGF-dependent effect. This has been first evidence for the fact that endometriotic
lesions induce neurite sprouting and therefore modulate the nervous system.
2.2.2.1.2.4. Modulation of Peritoneal Innervation

In general, the nerve fiber density in peritoneal lesions of endometriosis patients appears
to be higher compared to the peritoneum of patients without endometriosis (Tokushige, et al.
2006). Progestogens and combined oral contraceptives reduced nerve fiber density in
peritoneal endometriotic lesions (Tokushige, et al. 2009). but it does not reach the low density
of nerve fibers in healthy woman. This indicates that beside to the neurotrophic properties of
the endometriotic lesion itself the neuromodulation is also a hormone-dependent
phenomenon, but other factors like local cytokines released by macrophages also seem to
influence it. Nevertheless, in another study including patients who received hormonal therapy,
they again became symptomatic, and nerve fibers in close contact with the peritoneal lesions
could be detected (Mechsner et al., 2008). The neuro-modulatory processes seem to succumb
to hormone-dependent regulation but independent from the cyclic phases, since locally
increased levels of estrogen, caused by an aromatase overexpression, leads to uterine
remodelling, independent from cyclic phases (Sporrong, et al. 1981, Yamada 1988).
2.2.2.1.3. Neurogenic Inflammation

Suitably, those potential endometriosis-associated neuromodulatory properties go with
the concept of neurogenic inflammation (Vercellini, et al. 2009, Barcena de Arellano, et al.
2010).
Autonomic and somatic nerve fibers, in particular SP positive C-fibers are closely
associated with immune cells, especially with mast cells. Those nerve fibers release SP and
other neuropeptides (for example CGRP, neurokinin A/ B and somatostatin), which are
involved in inflammatory processes. Inflammatory processes promote the synthesis of nerve
growth factors like NGF and lead to an upregulation of the corresponding receptors
(NGFRp75 and Trk-A), which stimulate both the growth of nerve fibers, as well as the
degranulation of mast cells, with the release of PG, IL, TNF, TGF1, H, 5HT with a
corresponding activation of nociceptors on sensory nerve fibers (Vercellini, et al. 2009). This,
therefore, promotes the inflammatory response.
Estrogens also appear to have an influence on the formation of the peripheral neurogenic
inflammation and modulate central sensory stimuli (Lamvu, et al. 2006). In agreement with
that, macrophages with high affinity for endometriosis-associated nerve fibers could be found
in peritoneal lesions (Tran, et al. 2009). Macrophages were also detectable in macroscopically
inconspicuous peritoneum of patients with endometriosis, so that the accumulation of
macrophages and the release of their products may be involved in the development of
endometriotic lesions (Tran, et al. 2009).
2.2.2.1.4. Neuromodulation in Endometriosis

Pain generation in endometriosis is the result of a complex interaction of several
parameters like endometriotic stromal and epithelial cells, nerve fibers and cytokine releasing
immune cells, but also macrophages and mast cells. These interactions might induce a
neurogene inflammatory process (Vercellini 1997). Peritoneal endometriotic lesions are
involved in the production of several pain-mediating substances like prostaglandin E2/F2,
histamine, kinins, NGF and different interleukins (IL), which can activate peritoneal
nociceptors (Vernon, et al. 1986, Drake, et al. 1981, Moon, et al. 1981, Jones 1982).
Simultaneously, those pain-mediating factors induce the release of more histamine,
prostaglandins (PGs), serotonin, bradykinin, IL, vascular endothelial growth factor (VEGF),
transforming growth factor-beta (TGF), tumour necrosis factor-alpha (TNF) and NGF
from macrophages and mast cells. Macrophages are found with high affinity to endometriotic
lesions (Tran, et al. 2009). In response to these inflammatory activity, sensory nerve-endings
release neurotransmitters like SP, calcitonin gene-related peptide (CGRP), endothelin,
histamine, glutamate, PG and vasoactive intestinal peptide (VIP) (Mantyh 2002). These
substances support the already persisting activation and immigration of further immune cells
in an area affected with endometriosis. The resulting neurogene inflammatory reaction (the
interplay of endometriotic lesion, immune cells and nerve fibers) leads to pain generation and
to an induction of nerve fiber sprouting around the lesions. In addition, nerve damage and
irritation caused by these events are also considered leading to a neuropathic pain component.
2.2.2.1.5. Endometriosis-Associated Smooth Muscle Cells

In addition to epithelial and stromal cells, smooth muscle cells are also found in
peritoneal endometriotic lesions (Mechsner et al., 2005). Endometriosis-associated smooth
muscle cells occupy significant proportion (40%) of the lesion (Barcena de Arellano, et al.
2011).
Peritoneal endometriotic lesion- associated smooth muscle cells (pEMaSMC) express the
oxytocin receptor, both estrogen receptors and the progesterone receptor, which are all
components characterising uterine myometrial cells (Gimpl, et al. 2001), but the ability to
show contraction and other myometrial-cell-like functions are still not verified. It seems to be
possible that pEMaSMC contractions stimulate peritoneal nociceptors, leading to pain
generation (Gimpl, et al. 2001, Burns, et al. 2001).
2.2.2.2. Adhesions
Adhesions are also considered as a mechanism of pain-pathogenesis. Endometriosis-
associated adhesions develop within the progression of the disease and possibly reflect the
transition of the cyclic pain into acyclic chronic pain. The importance of adhesions and post-
operative adhesions as a cause of chronic pelvic pain is critically discussed for many years. A
prospective study showed that the pain reduction through adhesiolysis is not significantly
improved compared to sole diagnostic laparoscopy (Swank, et al. 2003). Nevertheless, the
evidence regarding the etiology of pain is unclear. There is an agreement that endometriosis is
a chronic inflammatory disease associated with pelvic adhesions (Daniel, et al. 2000), and
that pelvic adhesion occur even after laparoscopic excision of endometriotic lesions and
adhesiolysis (Gurgan, et al. 1996, Parker, et al. 2005, Luciano, et al. 2008). It has been found
that the levels of interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-a in peritoneal
fluid are correlated with the degree of pelvic endometriosis associated adhesions (Cheong, et
al. 2002), suggesting the contribution of inflammatory cytokines and growth factors to the
formation of pelvic adhesions (Cheong, et al. 2002, Cheong, et al. 2003, Cheong, et al. 2002).
In women with endometriosis, pelvic adhesions contain estrogen and progesterone receptors,
and produce basic fibroblastic growth factor and vascular endothelial growth factor, implying
a regulation of pelvic adhesion formation by steroid hormone (Jirasek, et al. 1998, Schindler
2004) Adhesions related pain seems to be a rather gynaecological problem, occurring almost
exclusively in women, although adhesions can also occur in men (Hammoud, et al. 2004).
Perhaps if the internal genital organs of women are affected by adhesions, they are more
sensitive to pain. In addition, hormonal factors may be added, so as the mast cell
degranulation (release of pain mediators) is an estrogen-depending process, occurring
particularly in women (Hammoud, et al. 2004). Furthermore, the detection of sensory nerve
fibers in post-operative, endometriosis-associated adhesions suggests an involvement in the
pathogenesis of pain (Sulaiman et a., 2001, Tulandi et al., 1998)
2.2.2.3. Uterus
That not only peritoneal lesions are involved in the development of pain, shows the work
of Parker et al. Pelvic pain could still be detected after optimal excision of all endometriotic
lesions of the pelvis. These occurred particularly when adenomyosis was present. This is an
indication that the uterus itself is involved in the sensation of lower abdominal pain and that it
is difficult to differentiate uterine and pelvic pain (Parker, et al. 2005).
2.2.2.4. Musculoskeletal System

Pelvic pain can arise from muscles of the pelvic floor as well as from muscles of the
abdonimnal wall. There is an increasing recognition that spasms of these muscles can be
primary or secondary causes of pelvic pain. Up to 85% of patients with chronic pelvic pain
have musculoskeletal dysfunctions like muscular spasm of the pelvic floor (Baker 1993,
Prendergast, et al. 2003). Due to chronic pain, patients with endometriosis often also have
pelvic floor spasms.
2.2.3. Deep Dyspareunia
2.2.3.1. Neuronal Dysfunction Caused by Tissue Damage and Reinnervation

Persistent straining for example to achieve defaecation promotes tissue defects leading to
a denervation, especially in the uterosacral ligaments. This damage interrupts normal patterns
of uterine contractility and causes retrograde menstruation, adhesion and implantation of
ectopic Endometrium and therefore leads to the manifestation of endometriosis and its
symptoms, like subfertility and pelvic pain (Quinn 2004, Sampson 1927). The reinervation
phenomenon with following neuronal dysfunction could also be observed in other painful
diseases with tissue damage (Lerner, et al. 1985, Quinn 2004, Westrom, et al. 1998, Quinn, et
al. 2002, Christmas, et al. 1990)
2.3. Management of Endometriosis-Associated Pain (Without Current

Desire for Pregnancy)
First, an accurate and meticulous patient history is important. And a detailed,

chronological history of pain must be obtained. This should included time, onset and nature
of pains as well as its location, radiation, precipitation and relieving factors. The physician
especially has to ask for dysmenorrhea, pelvic pain (cyclic and acyclic), deep dyspareunia,
dyschezia and dysuria. The menstrual background is an essential part of the history, with
particular attention to cyclic pain. The onset of associated symptoms, such as dysuria or
change of bowel habit in relation to the menstrual cycle should be determined. The severity of
symptoms has to be discovered in a questionnaire with a visual analogue scale. Furthermore,
associated symptoms like the unspecific bowel symptoms have to be assessed. Under
consideration of the endometriosis-typical history, the overlap with symptoms of other
gynaecological and non-gynaecological conditions (with dysmenorrhea or pelvic pain) can be
avoided. The physical examination should include a pelvic examination and a vaginal
ultrasound. Focal tenderness in pelvic examinations is highly associated with endometriosis.
A pelvic mass, immobile pelvic organs and rectovaginal nodules are also indicative for
endometriosis.
In case of a suspected endometriosis, a diagnostic laparoscopy with removal of all visible
endometriotic implants has to be performed. This is also the first step for the clinical staging
(rASRM 1997). The removal of visible implants and endometriotic nodules with a combined
restoration of the anatomy and an adhesiolysis is the first important step of treatment. Several
studies could demonstrate a significant pain reduction and improvement of the quality of live
after laparoscopic lesion excision (Jacobson, et al. 2009, Hart, et al. 2005, Garry 2004),
especially in cases of deep infiltrating endometriosis (Chapron, et al. 2003)
The main problem of endometriosis is the chronic character of the disease with a high
recurrence rate of symptoms and implants after surgical treatment (Vercellini, et al. 2008). In
most cases, if symptoms are persisting, a hormonal treatment is necessary. Under
consideration of the patients desire of future fertility, side effects profile, and personal
preference, the best medical treatment for endometriosis include COCs and POPs in their
various forms, since they may be used in long term, have acceptable side effects profiles and
create low costs. The use of COCP on a continuous basis is effective in arresting the
menstruation, thus preventing dysmenorrhea and cyclical pelvic pain. Progestogens have a
variety of mechanisms of action, including suppression of ovarian activity, and have been
demonstrated to be a very effective drug for endometriosis patients (Vercellini 1997). A new
therapeutic approach is the usage of levonorgestrel releasing device, especially for the
treatment of dysmenorrhea (Bayoglu Tekin, et al.). GnRH analogues can be used to suppress
ovarian function and therefore result in a relief of the pain symptoms of endometriosis
patients.
The symptomatic treatment with painkiller alone like prostaglandin inhibitors (ibuprofen)
is possible, if it works.
In cases of a pain recurrence after surgical treatment, with an inconspicuous pelvic
examination, hormonal treatment should be induced. The indication for recurrent surgery
treatment is a difficult decision, since the extent and duration of the positive effect of
secondary surgery is still unclear (Vercellini, et al. 2009). The decision for a recurrent surgery
should be done under consideration of the efficacy of the first surgery treatment, visible or
palpable endometriotic mass and the family planning situation. Re-Operation (in cases of an
inconspicuous pelvic examination) should be avoided as long as possible. A promising
effective treatment is an osteopathic intervention, as complementary treatment option,
especially for pelvic pain, adhesions, myofascial pain, and myalgia. Furthermore an
interdisciplinary observation of the patients is desirable (psychosomatic and pain polyclinic).
In summary, the patients suffering of endometriosis-.associated chronic pelvic pain,
resulting in severe discomfort with reduction of their quality of life, need long-term treatment
and in fact a very individual treatment with optimal finding of the suitable therapy.
Conclusion
Pain is a complex process, depending on different pain stimuli, transmission and central
processing, which is influenced by subjective variables of the pain cognition. These
mechanisms are accessible through various peptides. Other explanations for the pain
generation are urgently required, particularly since the benefits of surgical, hormonal or
analgesic therapies are sometimes poorly. Although a large number of patients are completely
asymptomatic after treatment.
There are in addition to the commonly accepted inflammatory, nociceptive pain
component of neuropathic pain, neurogenic inflammatory processes and myogenic pain
mechanisms that might explains the complex pathology of endometriosis-associated pelvic
pain, superiorly.
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Y. Bayoglu Tekin, B. Dilbaz, S. K. Altinbas,S. Dilbaz. Postoperative medical treatment of
chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine
system versus gonadotropin-releasing hormone analogue. Fertil Steril;95:492-6.
Chapter VI
Chronic Non Bacterial

Prostatitis/Chronic Pelvic Pain
Syndrome
Ahmed S. El Hefnawy, MD*

Voiding Dysfunction and Urodynamic, Urology and Nephrology Center,
Faculty of Medicine- Mansoura University, Mansoura, Egypt
Introduction
Chronic nonbacterial prostatitis/ Chronic pelvic pain syndrome (CP/CPPS) is a common
condition characterized by confluence of pain, infection, and voiding symptoms. Despite the
prevalence of these symptoms, etiology, pathogenesis of CP/CPPS remains unknown. In
addition, the optimal treatment for CP/CPSS is still lacking. The name chronic pelvic pain
syndrome recognizes that the prostate may not be the sole source of discomfort, and that
there may be other factors or anatomic sites involved.
In this chapter we discuss one of enigmatic causes of chronic pain, CP/CPSS.
Historical Definitions and Recent Classifications

For the most of last century, direct interpretation of prostatitis was an inflammation and
or infection of the prostate (Nickel, 1999). In 1978, Drash and collegues (Drash et al, 1978)
developed 4 entities classification that entailed acute prostatitis, chronic bacterial prostatitis,
chronic non-bacterial prostatitis, and prostatodynia. Because of heterogeneity of prostatitis
symptoms and multiple questions about the definitive pathophysiology of prostatitis, there
have been continuous evolutions in research field. For standardization of terminology and
* E mail: a_s_elhefnawy@yahoo.com.
152 Ahmed S. El Hefnawy
methodology of research, the NIH International Collaborative Prostatitis Network developed

a new prostatitis classification system in 1995 (Krieger et al, 1999). NIH classification based
solely on presumed etiology and clinical findings, including culture and microscopic findings
from expressed prostatic secretions, preprostatic and postprostatic massage urine sediment, or
semen analysis. In NIH classification, prostatitis has been categorized into four clinical
entities, with category III incorporating chronic non-bacterial prostatitis/chronic pelvic pain
syndrome (CP/CPPS).
Table 1. NIH classification of prostatitis
Category Description/ Type Characteristics

I Acute bacterial prostatitis Associated with severe pain symptoms,
systemic infection, and acute bacterial
urinary tract infection.
II Chronic bacterial prostatitis Caused by chronic bacterial infection of the
prostate and recurrent symptomatic
episodes, usually with recurrent urinary tract
infections caused by the same bacteria.
III Chronic prostatitis/ chronic pelvic Characterized by symptoms of chronic
pain syndrome pelvic pain and possibly symptoms of
voiding in the absence of urinary tract
infection. This category is subdivided into
inflammatory (IIIA) and non-inflammatory
(IIIB) prostatitis.
IV Asymptomatic inflammation Characterized by evidence of inflammation
of the prostate of the prostate in the absence of
genitourinary tract symptoms; an incidental
finding during evaluation for other
conditions, such as fertility or elevated PSA
levels.
Category III (CP/CPPS) comprises the vast majority of prostatitis cases (90%95%) and
further subdivided into inflammatory (IIIA) and noninflammatory (IIIB) prostatitis based on
the presence or absence of leukocytes in the expressed prostatic fluid or ejaculate (Le and
Schaeffer, 2009). This corresponds to the previously used classification of nonbacterial
prostatitis. Category IIIB is comparable to the formerly used term prostatodynia, and
refers to patients with pelvic pain but no evidence of inflammation on semen, VB3, or EPS.
The symptom that distinguishes CP/CPPS from other voiding dysfunction is the presence of
pain (Krieger et al, 1996).
There is recent evidence that Category III (CP/CPPS) is accompanied by alterations in
immunological parameters that may indicate a chronic inflammatory process in Category IIIA
as well as IIIB patients (Maake and John, 2003). However, even extensive research has not
yet been able to produce conclusive evidence as to the essential differences between the two
categories and the consequences of these immunological changes in terms of diagnosis,
treatment and prognosis (Hedelin and Fall, 2008). Furthermore, the symptoms and signs
associated with Categories IIIA and IIIB are indistinguishable. Consequently, the two groups
are mostly discussed and managed as one entity as the clinical relevance of the subgrouping
has limited or even no value in clinical practice (Nickel, 2006).
Chronic Non Bacterial Prostatitis/Chronic Pelvic Pain Syndrome 153
Epidemiology and Economic Burden

CP/CPPS is a highly prevalent condition. Estimates of CP/CPPS prevalence range from
2% to 10%, with overall lifetime prevalence estimated to be 9-16% (Nickel, 2007). The
differences may reflect variations in genetic risks, lifestyle, culture and socio-economic
status. Data published by National Ambulatory Medical Care Survey data for 8-year study
have shown age-adjusted outpatient visit rate 1,867 per 100,000 populations (Collins and
Pontari, 2007).
Until recently, In traditional concepts, prostatitis was considered a problem only in
younger men until recently, it was found to be affecting men of a wide age range. In the NIH
sponsored Chronic Prostatitis Collaborative Research Network (CPCRN) study, the mean age
was 42 years old but the age range was 20 to 83 (Schaeffer et al, 2002). In a Finnish study, a
questionnaire was sent to 2500 men aged between 20 and 50 years inquiring whether they had
at any time been diagnosed with prostatitis by a physician. The lifetime prevalence was found
to be 14.2%. An interesting finding was that 65% of men diagnosed with prostatitis were
most troubled during the winter time (November to March) (Mehik et al, 2000).
Economic impact of CP/CPPS is well studied. In a recent study the direct and indirect
costs of both IC/PBS and CP/ CPPS were assessed and compared. Approximately 80% of
patients IC/PBS reported direct medical costs in the preceding 3 months that were attributed
to their pelvic pain symptoms Using Medicare rates, the mean yearly cost for CP/CPPS was
$3017 per person. However, use of more accurate non-Medicare, mean yearly per person
costs CP/CPPS increase to $6534. While indirect cost was 3248 per person with CP/ CPPS.
These costs are similar or greater than those reported for other chronic pain conditions such as
peripheral neuropathy ($1087), low back pain ($4256), fibromyalgia ($3784) and rheumatoid
arthritis ($6710)1013(all costs adjusted to 2005 U.S. dollars) (Clemens et al, 2009).
Etiology and Pathogenesis

Identifying exact etiology and understanding the possible pathogenetic mechanisms
underlying each patient's symptoms is crucial for choosing effective therapy.
The exact etiology of CP/CPPS is still unknown. Current etiologic hypotheses vary
widely. These include the presence of antibiotic-resistant non-culturable microorganisms,
urethral obstruction, reflux of urine in the prostatic ducts, autoimmune attack, genetic
abnormalities, pudendal nerve entrapment. In a number of patients, myofascial pain or
dysregulation of pelvic floor muscles, and neuropathic pain may also be the origin of the
troublesome symptoms. There is recent trend that CP/CPPS are caused by an inter-related
cascade of inflammatory, immunologic, neuro-endocrine, and neuropathic mechanisms that
begin with an initiator (perhaps an initial infection) in a genetically or anatomically
susceptible man. In many or most cases the pathology extends beyond the prostate
gland itself.
Infection
One of the most prevalent theories as to the development of symptoms in CP/CPPS is

that of an occult or undertreated infection. One of the supporting factors of this theory is
similarity between symptoms of CP/CPPS those of a true prostatic infection. In population
cohort study of over 30,000 male health professionals, in which those men reporting a history
of sexually transmitted disease had 1.8-fold greater odds of a self-reported history of
prostatitis (Collins et al, 2002). This interesting finding supports the speculation about
presence of acute infection as a trigger to develop CP/CPPS.
On the other hand, it seems unlikely that the theory of an ongoing acute infection is
supported on an objective basis. Particularly intriguing is the finding of cultures localizing
uropathogenic bacteria to the prostate in 8% of asymptomatic men with CPPS, and what are
considered to be nonuropathogens in 74% of asymptomatic age matched controls (Nickel et
al, 2003a). This suggests that the prostate of normal asymptomatic males harbors bacteria.
Data is still lacking about possible role of microorganisms that are not detected in ordinary
culture and bacterial bio-film which is resistant to antibiotics.
There have been multiple reports of abnormal level cytokines in expressed prostatic
secretion (EPS) and seminal plasma, including interleukin (IL)-8, IL-10 IL-1B and tumor
necrosis factor (TNF)-a. However, although there have been differences shown between
CP/CPPS patients and controls, there has been no consistent pattern across all studies
(Hochreiter et al, 2000; Miller et al, 2002; Nadler et al,2000; Pontari,2008).
Alteration of Urinary Flow and Stroma Involvement
Recently, Dellabella and colleagues demonstrated the presence of a set of

ultrasonographic lesions, particularly in the bladder neck, proximal urethra, and in the
anterior fibromuscular stroma in patients with CP/CPPS (Dellabella et al, 2006). In these
areas, they found thickened hyperechoic fibers, strongly suggesting the presence of possible
hypertrophy fibrosis and hyperplasia of the fibromuscular component of the prostate. The
involvement of the periurethral smooth muscle cells, the anterior fibromuscolar stroma, and
the bladder neck muscle fibers, which are anatomically contiguous and compose the
preprostatic sphincter (Villers et al, 1990). The hypertrophy and hyperplasia of this sphincter
could lead to spasm, painful contracture, and subsequent alteration in the urinary flow. These
findings strongly suggest a prevalent stromal involvement, specifically of the smooth muscle
cells, in CP/CPPS physiopathology (Dellabella et al, 2009).
Central Sensitization and Neurologic Dysfunction
Recently, there is tendency in the literature to a concept that pain of CP/CPPS is a result
of central neurological dysfunction rather than merely to be a symptom of peripheral organ
disease. The presence of central sensitization in patients with CPPS was demonstrated by
Yang and colleagues who compared thermal algometry in men with CPPS and asymptomatic
controls (Yang et al, 2003). Sensitivity to noxious heat stimuli is thought to be a reflection of
central sensitization. The men with CPPS reported a higher visual analog scale to short bursts
of noxious heat stimuli to the perineum, but no difference to the anterior thigh. Thus, these
patients have altered sensation in the perineum when compared with controls.
Functional magnetic resonance studies for evaluating patients with CPPS and interstitial
cystitis show distinct patterns in bilateral anterior insula and anterior cingulate cortex in
patients experiencing chronic pelvic pain (Schaeffer et al, 2009).The possibility of
impairment of anti-nociceptive pathways due to deficiencies in the serotonergic/noradrenergic
pathways, such as those present in chronic fibromyalgia, is a question that warrants
exploration in CPPS/PPS, as it would have immediate therapeutic implications (Dadabhoy
and Clauw, 2005). That there is an altered autonomic nervous system response in men with
CPPS/PPS has also recently been reported (Yilmaz et al, 2007).
Genetic Theory
Recent studies have identified special genetic entities in patients with CP/CPPS.
Differences in the DNA sequence or polymorphisms have been identified in the promoter
regions of several cytokines. In a recent study, significantly more men with CPPS expressed
the IL-10 AA genotype compared with controls (11 of 36 or 31% versus 33 out of 272 or
12%; P <.007) (Shoskes et al, 2002).All eight IIIA patients had the low TNF-a production
genotype. There was no difference in the TNF-a genotype in the 22 IIIB patients versus 272
controls, but all eight of the IIIA patients had the low TNF-a genotype. Bacterial 16S rRNA
genes and expression of IL-1, TNF- and Ig A in prostate tissues have been investigated
with possible association to chronic prostatitis (Xie et al, 2010). Vidas (2010) reported
polymorphisms in Toll-like receptor genes implications for prostate cancer development.
Cold
With the exception of cold tissue injuries, there has not been much research concerning
cold as an etiological agent. It is well established that thermal stimuli affect the function of
the lower urinary tract. The bladder and urethra are supplied with specialized cold receptors
constituting a segmental cooling reflex mediated by C-fibres (Geirsson et al, 1999).
Agrreviation of symptoms in patients with CP/CPPS have been reported in many studies
(Mehik et al, 2000; Hedelin and Jonsson, 2007). One possible explanation is vasoconstriction
within the prostate and intraprostatic urethra. Another possibility being that the intraprostatic
and/or pelvic floor musculature are involved in terms of a cold-induced muscle spasm. The
third possibility is that in a state of allodynia and hyperalgesia, cold may not be perceived at
all as in a healthy individual, but is instead experienced as pain. A combination of
hypersensitivity and exaggerated vasoconstriction is yet another possibility (Hedelin and Fall,
2008).
Reflux of Urine
It has been proposed that intraprostatic reflux of urine (especially urate) results in a
chemical injury to the epithelium that initiates an immunological reaction, a possible starting
point for chronic inflammation (Kerby et al, 1982; Persson and Ronquist, 1996).
Nevertheless, this concept has not been followed up and has not resulted in therapeutic
achievements.
CP/CPPS and Psychological Disorders

Pain encountered in CP/CPPS leads to dramatic negative impact on quality of life. Pelvic
pain in CP/CPPS is dependent upon helplessness, catastrophizing, and depression (Tripp et al,
2006). Reciprocally, psychologic factors also appear to be involved in producing symptoms in
men with CP/CPPS and psychologic stress is a common finding in men with CPPS (Mehik et
al, 2001). The ultimate result of this interactive relationship is a vicious circle that induces
more psychological disorders and intensifies pain perception. In a prospective study, 200
patients with CP/CPSS were examined for whether perceived stress was associated
longitudinally with pain intensity and pain-related disability (Ullrich et al, 2005). Results
have shown greater perceived stress during the 6 months after the health-care visit was
associated with greater pain intensity and disability at 12 months.
Prostatitis and Prostate Cancer

Direct causal relationship between chronic prostatitis and prostate cancer has not been
proven. However, several studies reported common association between both pathologies.
Delongchamp and co workers investigated such association in a prospective analysis of 167
autopsied prostate. Results revealed that chronic inflammation was directly associated with
benign prostatic hyperplesia but not with cancer (Delongchamp et al, 2008). Vav3 oncogene
is overexpressed in human prostate cancer, activates androgen receptor (AR), and stimulates
growth in prostate cancer cells. Liu and colleague demonstrated that Vav3 overexpression in
the prostate epithelium enhanced both the AR signaling axis and NF-kappaB-mediated
pathway, which potentially contributed to the development of nonbacterial prostatitis and
prostate cancer (Liu et al, 2008).
CP/CPPS and Sexual Dysfunction

The vast majority of CP/CPPS research ignores sexual dysfunction (SD). In addition
there are multiple limitations of reports which addressed the issue of SD in cases with
CP/CPPS. One of these limitations is that about one-third use custom self-report measures
which have not been standardized. In those studies that do use standardized questionnaires,
there are a number of different measures. The most common is the International Index of
Erectile Functioning (IIEF) (Davis and Binik, 2009).
Erectile dysfunction (ED) is not uncommon in men with CPPS/PPS. Reported erectile
dysfunction prevalence findings for CPPS sufferers vary greatly, ranging from 0.6% (Collins
et al, 1999) to 48.3% (Lee et al., 2008). In cross sectional investigation in study from China
(Hao et al, 2011), reported prevalence was 40.5%. This large discrepancy is likely due to
inconsistent measurement, and varying methods of sampling (Davis and Binik, 2009). Many
factors can impact erectile functioning, including vascular deficiency, nerve damage, pain,
and psychosocial difficulties. Gonen and co workers used penile doppler in patients with
CP/CPPS and ED to rule out any vascular abnormities as a possible physical etiological
factors (Gonen et al, 2005). None of these patients showed evidence of vascular deficiency
that would interfere with the ability to get an erection; this led suggestion that a psychogenic
factor is a possible cause, although neurological and hormonal causes were not ruled out. As a
whole, the association may quite likely be due to a secondary effect mediated by negative
influences on quality of life and self-esteem (Muller and Mullhal, 2005).
In men with CP/CPPS, depressive symptoms appear to have a negative effect on orgasm,
sexual satisfaction, and measures of sensuality (Smith et al., 2007), as well as lowering the
frequency of sexual activity and more difficulty achieving orgasm (Aubin et al., 2008).
Premature ejaculation has been shown to be very common in men afflicted with
CPPS/PPS (Davis and Binik, 2009). This has, however, not been verified in other studies .A
more distinct association between the two conditions is still questionable and one of the
issues that merits further study.
Painful ejaculations are a very common complaint among men afflicted with CPPS/PPS,
but their correlation with ED in CPPS/PPS remains controversial.
The effect of ejaculation itself on CP/CPPS symptoms is not fully known. Although pain
with ejaculation is considered as bother symptom for CP/CPPS, at least one small study found
positive effects of ejaculation for men who did not ejaculate regularly (Yavascaoglu et al,
1999). However, two others found either no effect, or that ejaculation worsened symptoms
(Aubin et al., 2008; Turner et al, 2006). Nonetheless, patients with CP/CPPS have rate
ejaculation as a first choice when they were asked to rate activities that they found most
helpful to relieve pain (Turner et al., 2006).
Diagnosis
CP/CPPS is involving local symptoms (pelvic pain localized to the prostate, perineum, or
urethra, urinary voiding symptoms, and ejaculatory symptoms); no identifiable uropathogen
or infectious cause. There is no accepted standard evaluation for men with CP/CPPS.
Mandatory measures include a history, physical examination (including digital rectal
examination and urinalysis), and urine culture (Nickel, 2002).
History
History should include previous UTI, sexually transmitted diseases, past lower urinary
tract problems, and previous urologic instrumentation and surgery. The most important
history is comprised of a discussion of the pain (location, severity, and frequency), voiding
symptoms (obstructive and irritative), and the impact this condition is having on the patients
activities and quality of life (Touma and Nickel, 2011).
In 1999, the NIH Chronic Prostatitis Collaborative Research Network (CPCRN)
developed an instrument to measure the symptoms and quality of life of CPPS for use in
research protocols as well as clinical practice. The result of this effort is the NIH Chronic
Prostatitis Symptom Index (NIH-CPSI), which is administered as a questionnaire and has
subsequently been validated in several studies (Litwen et al, 1999). In addition to evaluation
of pain, the questionnaire also evaluates lower urinary tract symptoms, impact of symptoms,
and quality of life impact Fig-1. (NIH-CPSI) has become currently the gold standard for the
diagnosis of CP/CPPS (Strauss and Dimitrakov, 2010) with recommendations to be
incorporated into the evaluation to quantify initial symptoms and monitor response to therapy
(Lie and Schaeffer, 2009). However, some authors believe that despite its apparently robust
discriminative abilities, should caution should be followed before using it as a screening or
diagnostic tool (Litwen et al, 1999; Hedelin and Fall, 2008).
Pain or Discomfort 6. How often have you had to urinate again less than two
1. In the last week, have you experienced any pain or hours after you finished urinating, over the last week?
discomfort in the following areas? 0 Not at all
Yes No 1 Less than 1 time in 5
a. Area between rectum and 1 0 2 Less than half the time
testicles (perineum) 3 About half the time
b. Testicles 1 0 4 More than half the time
c. Tip of the penis (not related to 1 0 5 Almost always
urination) Impact of Symptoms
d . Below your waist, in your 1 0 7. How much have your symptoms kept you from doing
pubic or bladder area the kinds of things you would usually do, over the
2. In the last week, have you experienced: last week?
Yes No 0 None
a . Pain or burning during 1 0 1 Only a little
urination? 2 Some
b . Pain or discomfort during or 1 0 3 A lot
after sexual climax (ejaculation)? 8. How much did you think about your symptoms, over
3. How often have you had pain or discomfort in any of the
these areas over the last week? last week?
0 Never 0 None
1 Rarely 1 Only a little
2 Sometimes 2 Some
3 Often 3 A lot
4 Usually Quality of Life
5 Always 9. If you were to spend the rest of your life with your
4. Which number best describes your AVERAGE pain or symptoms just the way they have been during the last
discomfort on the days that you had it, over the last week? week, how would you feel about that?
0 Delighted
0 1 2 3 4 5 6 7 8 9 10 1 Pleased
NO PAIN AS PAIN BAD AS YOU CAN IMAGINE 2 Mostly satisfied
Urination 3 Mixed (about equally satisfied and dissatisfied)
5. How often have you had a sensation of not emptying 4 Mostly dissatisfied
your bladder completely after you finished urinating, 5 Unhappy
over the last week? 6 Terrible
0 Not at all ______________________________________________
1 Less than 1 time in 5 Scoring the NIH-Chronic Prostatitis Symptom Index
2 Less than half the time Domains
3 About half the time Pain: Total of items 1a, 1b, 1c, 1d, 2a, 2b, 3, and 4 =
4 More than half the time ____
5 Almost always Urinary Symptoms: Total of items 5 and 6 = ____
Quality of Life Impact: Total of items 7, 8, and 9 = ____
Figure 1. NIH- Chronic Porstatitis Symptom Index NIH-CPSI.

Physical Examination
The physical examination is an important part of the evaluation of CP/CPPS, although it

is usually unhelpful in diagnosing or further classifying it. The physical examination consists
of an abdominal examination (including suprapubic area), followed by careful examination
and palpation of the groin, spermatic cord, epididymis, and testes. The clinician is looking for
areas of pain/discomfort, for unexpected masses, and for the possibility of urinary retention.
Digital Rectal Examination (DRE): Although there is no pathognomonic sign for
CP/CPPS in DRE, however, it should be done specially in elderly patients .The absence or
presence of tenderness should, however, not be allowed to play a pivotal role in the diagnostic
procedure. That the gland is not always tender in men with CPPS/PPS is indirect evidence of
the fact that an inflammation within the gland is not the cause of the condition; inflammatory
involvement ought to be associated with a tender prostate (Hedelin and Fall, 2008). DRE also
includes palpation of the perineum, pelvic floor, and pelvic sidewalls noting any muscle
spasm or myofascial tenderness (Touma and Nickel, 2011).
Laboratory Investigations
Figure 2. Four glasses (Meares Stamey) test.
The four-glass localization Test: While in acute prostatitis , expressed prostatic secretions
(EPS) should not be obtained because of the theoretical concern for worsening sepsis , it plays
detrimental role in diagnosis of other types of prosatitis. NIH classification is based on the
results of the four-glass (Meares stamey) localization cultures Fig-2. In Meares-Stamey four-
glass test, the first 10 mL of urine (VB1) representing the urethral flora is collected. Then a
midstream urine culture (VB2) representing the bladder flora is collected. At this point the
physician performs a prostatic massage and collects the expressed prostatic secretions (EPS).
The first 10 mL of urine after prostatic massage (VB3) is then collected. All are sent for
culture and microscopic analysis. Expressed prostatic secretions are considered positive if
there is a 10- fold increase in uropathogen count (i.e., colony forming units per milliliter)
compared with VB1 and VB2 Table-2. The 4-glass or 2-glass tests and the ejaculate test can
be used to distinguish between the inflammatory and non inflammatory forms (Weidner and
Anderson, 2008). The exact limits in the ejaculate for distinguishing between inflammatory
and noninflammatory CP/CPPS are currently being discussed Table-3 (Ludwig et al,
2003;Penna et al, 2007; Florian et al, 2009). However, in routine practice, obtaining cultures
from expressed prostatic fluid is rare, although this may be indicated in research situations,
one limitation being the difficulty of obtaining a sample (Pvone, 2007).
Table 2. NIH Classification of Prostatitis Syndrome
NIH Bladder Urine Midstream (VB2)Expressed Prostatic Secretion

Classification Specimen
Culture WBC Culture WBC
I + + Not
recommended
II 0 0 +a +b
IIIa 0 0 0 +c
IIIb 0 0 0 0
IV
WBC: white blood cell count, a: Required, b: Not required, C: About 50% of patients have WBC in
expressed prostatic secretion.
Table 3. Current thresholds of the Giessen prostatitis clinic for the diagnosis of
CP/CPPS (CP/CPPS IIIa versus CP/CPPS IIIb) (Florian et al, 2009)
CP/CPPS IIIa CP/CPPS IIIB

Expressed prostatic secretion 1020/1000 <1020/1000
Post prostatic massage urine 10/mm3 <10/mm3
Ejaculate PPL 0.113 106 PPL/mL <0.113 106 PPL/Ml
Elastase 280 ng/mL <280 ng/mL
IL-8 10 63019 501 pg/mL 20335287 pg/mL
PPL, peroxidase-positive leukocytes; elastase, leukocyte elastase; IL-8, interleukin 8.
PSA: In one study addressing this issue (Nadler et al, 2006) a statistically significant
elevation of serum prostate-specific antigen (s-PSA) was registered. However, the increase
was minute and s-PSA should not be seen as a useful adjunct to the diagnosis of CPPS/PPS.
Need for New Markers?
Traditionally, white blood cells (WBCs) in the prostatic fluids have been studied and
thought to be markers for an inflammatory process that contributes to the symptoms of
prostatitis. The use of WBCs as markers of inflammation is limited for several reasons.
WBCs can be found in the prostatic fluid or seminal plasma of asymptomatic men, as well as
those with pelvic pain. In addition, in symptomatic men, none of the measures of the NIH-
chronic prostatitis symptom index (NIH-CPSI), including subsets for pain, urinary, and
quality of life, show any correlation with WBCs in EPS, VB3, or seminal plasma. Another
argument against the association between inflammation and symptoms is that category IIIB
patients have symptoms but no inflammation (Pontari, 2008).
In a study designed to systematically characterize prostate inflammation in patients who

satisfied strictly defined clinical and laboratory criteria for CP/CPPS showed no correlation
between expressed prostate secretions and histological inflammation. Inflammatory cells are
predominantly mononuclear, sparse, and widely distributed in a diffuse stromal pattern (16%
of patients) (True et al, 1999).
The secondary role of epithelial inflammation in the pathogenesis of CP/CPPS is also
supported by other results showing a poor correlation between inflammation in the semen and
in the expressed prostate secretions in patients with nonbacterial prostatitis, as well as the
finding that no correlation exists between the number of inflammatory cells in the ejaculate
and the degree of inflammation of the prostate parenchyma in a group of infertile or subfertile
men with prostatitis (Krieger et al, 1996; Dellabella et al, 2009).
Other diagnostic approaches: As today the diagnosis is essentially based on subjective
parameters, having excluded other causes of symptoms, the development of objective means
of diagnosis is desirable. One recent example of the way forward is the recording of
intraprostatic pressures. Studies have shown that the intraprostatic pressure is elevated in
CPPS/PPS (Mehik, 2002). The recording of intraprostatic pressure is an invasive procedure
that requires special equipment, which is an obvious but surmountable disadvantage. The use
of this method may be helpful but requires further validation, explanation of the causative
mechanisms (what is an elevated intraprostatic pressure actually mirroring?) and evaluation
of the general utility of the method, as it focuses merely on the prostate gland (Hedelin and
Fall, 2008).
Table 4. Six domains of UPOINT Classification
Domain characteristics
Urinary CPSI urinary score > 4
Patient complaint of bothersome urgency, frequency, or nocturia
Flow rate < 15 mL/s and/or obstructed pattern
Postvoid residual urine volume > 100 mL
Psychological Clinical depression
Poor coping or maladaptive behaviour, e.g. evidence of catastrophizing
(magnification or rumination in regard to symptoms, hopelessness) or
poor social interaction
Organ specific Specific prostate tenderness
Leukocytosis in prostatic fluid
Haematospermia
Extensive prostatic calcification
Infection Exclude patients with clinical evidence of acute (acute infection) or
chronic bacterial prostatitis recurrent infection that is localized to
prostate specimen between infections)
Gram-negative bacilli or enterococcus localized to prostatic fluid
Documented successful response to antimicrobial therapy
Neurological/sy Pain beyond abdomen and pelvis
stemic Irritable bowel syndrome
condition Fibromyalgia
Chronic fatigue syndrome
Tenderness of Palpable tenderness and/or painful muscle spasm or trigger points in
skeletal muscle perineum or pelvic floor or sidewalls during DRE examination
Phenotypic Classification of CP/CPPS: Upoint:
There is increasing awareness that patients with CP/CPPS individuals with different and
varying etiologies, progression pathways and response to therapy. This evokes the need to
find a new classification system that might lead to more proper diagnosis and consequently
more effective treatment of CP/CPPS.
Recently, classification system UPOINT has been adopted (Shoskes et al, 2009). It
entails 6 domains: Urinary, Psychosocial, Organ-specific, Infection, Neurological/ systemic,
Tenderness (of pelvic floor skeletal muscles). It was proposed that patients be classified into
one or more of these phenotypic domains as a way to characterize them and direct specific
therapy (Nickel and Shoskes, 2010).
Treatment
Until now, there are no formal guidelines for the management of CPPS and no proven
therapies. A wide variety of pharmacologic and non-pharmacologic therapies have been
studied in clinical trials, but most have shown limited curative efficacy in symptom
alleviation (Strauss and Dimitrakov, 2010). This plenty of published clinical trials does not
reflect only efforts to solve this prevalent enigmatic disease but it reflects that the etiology
and pathophysiology is still not understood.
Pharmacotherapy
Antibiotics
The results of antibiotics for treatment of CP/CPPS in controlled trials are mixed
(Pontari, 2008). Although less than 10% of CP/CPPS patients have definitive micro organism
in routine culture, long-term antibiotics were the mainstay of CP/CPPS treatment with
reported improvement of symptoms until recently. In culture-negative patients, these benefits
could result from the anti-inflammatory properties of antibiotics, the elimination of non
culturable microorganisms, or the placebo effect (Nickel, 2007).Antibiotics have also been
combined with treatment for prostatic stones to treat nanobacteria, and resulted in clinically
significant improvement in symptoms in a pilot study ( Shoskes et al, 2005) . However, there
is a common belief if the symptoms do not improve within two weeks, antibiotic therapy
should not be continued.
Recent RCTs have failed to show significant beneficial effects of antibiotics levofloxacin
and ciprofloxacin compared to placebo in patients who have already failed antibiotic
treatment (Nickel et al, 2003(b); Alexander et al, 2004). Further review of the patients
enrolled in those studies would show that they were very chronic (many years of symptoms or
since diagnosis), had many other treatments including previous antibiotic therapy in most, and
had seen numerous physicians for their condition (Nickel and Shoskes, 2010).
Alpha Blockers
The rationale for use of alpha blocker in CP/CPPS is based on the overlapping symptoms
of these conditions, such as voiding dysfunction, and the potentially overlapping
pathogenesis, such as sympathetic overactivation and endocrine imbalances. Alpha-blockers
have traditionally been postulated to inhibit overactivation of bladder neck smooth muscle
and thus increase urine flow, and more recently have been implicated in blocking
proliferation and inducing prostatic apoptosis (Yun and Doux, 2006; Anglin et al, 2002).
A metaanalysis of four alpha-blocker trials for CP/CPPS revealed overall benefit with
modest efficacy (Demitrakov et al, 2006). A recently completed multicenter, randomized,
doubleblinded, placebo controlled trial looking at alfuzosin for the treatment of chronic
prostatitispelvic pain syndrome showed no benefit over placebo (Nickel et al, 2008).
Overall, alpha blockers have been shown to give amelioration but their effect is rather
mediocre and what can be obtained is at best some symptom relief but no cure (Hedelin and
Fall, 2008).
5-Alpha Reductase Inhibitors
It promotes prostatic size reduction. Finasteride is an attractive medication to use in older

men with CP/CPPS because it also can be effective on benign prostatic hyperplasia, which
can be concurrent in men with symptoms of CP/ CPPS (Pontari, 2008). However, in two
RCT, Voiding symptoms did not improve significantly after using of finasteride (Nickel et al,
2004; Kaplan et al, 2004), which raises some interesting mechanistic questions. In a recent
report, dutasteride significantly (both statistically and clinically) reduced CP/CPPS symptoms
in men with prostatitis-like symptoms that were enrolled in a prostate cancer prevention trial
(Nickel et al, 2010).
Anti Inflammatory Agents
In an RCT of the COX2 inhibitor rofecoxib, the NIHCPSI total and pain scores showed
improvement in the rofecoxib group, but the difference between rofecoxib and placebo was
not statistically significant (Strauss and Dimitrakov, 2010). However, with the higher dose of
the cyclooxygenase-2 inhibitor, significantly more patients responded to 6 weeks of therapy
compared with placebo indicating that there was a clinical benefit in at least some of the
patients (Zeng et al, 2004).
Autoimmune mechanisms have been implicated in CP/CPPS, which suggests
corticosteroid therapy might be an attractive option (Tomaskovic et al, 2009). A recent RCT
involving combination prednisone and levofloxacin treatment for 2 or 4 weeks showed
statistically significant improvement in the treatment group compared to controls in several
outcomes, including NIH-CPSI and quality of life scores (Yang et al, 2009).
Pentosan Polysulfate
Pentosan polysulfate is a semi-synthetic mucopolysaccharide that may also have some

anti-inflammatory properties. A recent randomized placebo-controlled trial used 900 mg by
mouth every day for 16 weeks versus placebo: there was a moderate or marked clinical global
improvement with PPS, 36.7%, versus placebo, 17.8% (P < .04) (Nickel et al, 2005 a).
Standard dose therapy is 100 mg by mouth three times a day, and the dose of
pentosanpolysulfate appears less important than an adequate duration of therapy, which
should be at least 6 months (Nickel et al, 2005 b).
Neuromodulatory Therapy
Gabapentin and pregabalin are anticonvulsant drugs that have been used anecdotally in
patients with CP/CPPS. Pregabalin and gabapentin have relatively favorable adverse effect
profiles considering they are centrally acting drugs. In phase III trial, pregabalin did not show
significant improvement over placebo with regard to total NIH-CPSI score. However, all the
other important secondary outcomes (mean CPSI score, pain score, subjective responder rate,
etc.) were positive. Many patients did have a clinically favourable response despite the
negative conclusion of that RCT (Strauss and Dimitracov, 2010).
Several other centrally acting drugs have also been used include, Tricyclic antidepressant
Amitriptyline, opoids and and menantin with suggested potential for each of them to have a
therapeutic role
Amitriptyline is tricyclic antidepressant is thought to block pain by inhibiting the central
neuronal reuptake of norepinephrine and serotonin, potentiating the inhibitory effect of these
substances on the central pain processing receptor (Godfrey, 1996). More recent reviews of
treatment of neuropathic pain have suggested nortriptyline as first line therapy when using
TCAs, given its favorable side effect profile (Dworkin et al, 2003).
Opoids There are several reasons for avoiding the use of opioids in patients with chronic
non-cancer pain . The long-term use of opioids is associated with androgen deficiency and
sexual dysfunction and the even more unfavourable phenomenon of upregulation of pain
sensitivity. The overall result is that the patient may experience some pain relief but still
experiences no change, or even deterioration, in their quality of life (Hedelin and Fall, 2008;
Strauss and Dimitracov, 2010 ).
Herbal therapies: It is interesting to note that several clinical trials evaluating
untraditional therapies, such as phytotherapies (herbal-based compounds), did show efficacy
in randomized placebo controlled trials (Nickel et al, 2008). Quercetin was shown to be
superior to placebo in one small RCT (Shoskes et al, 1999). There are several trials
suggesting that pollen extract has beneficial effects in CP (Nickel et al, 2008), but it was only
the recently published German multicentre RCT that confirmed that the specific pollen
extract, Cernilton, was superior to placebo (Wagenlehner et al, 2009).
Botox: Intraprostatic injection of botulinum toxin A is currently being investigated in
these patients and may offer a new therapeutic approach (Gottsch et al, 2010).
Non Pharmacotherapy
A number of other procedures have been employed to treat men with CP/CPPS, including
transurethral microwave thermotherapy, transurethral needle ablation, spinal cord stimulation,
pudendal nerve block or decompression, transurethral prostate resection, electromagnetic
therapy and acupuncture.
Physical Therapy
Prostatic massage is the oldest traditional form of therapy for prostatitis. Evidence
supporting repetitive prostate massage therapy is conflicting, and a consensus panel
concluded that prostatic massage could be used as an adjunct form of therapy only in selected
patients. Frequent ejaculation may achieve the same (Mischra et al, 2008).Heat therapy;
physiotherapy massage; ischemic compression; stretching; anesthetic injections; acupuncture;
electroneural modulation; and mind-body interactions, such as progressive relaxation
exercises, yoga, and hypnosis, have all been tried, although more scientific scrutiny is
necessary to understand the role of these interventions in the treatment of CP/CPPS (Touma
and Nickel, 2011).
Myofascial Trigger Point Release
Pelvic pain manifests as a myofascial pain syndrome, in which abnormal muscular

tension could explain much of the discomfort and abnormal urinary dysfunction seen in this
disorder (Hetric et al, 2003). Genitourinary disorders such as voiding dysfunction and
ejaculatory pain are intimately related to the autonomic nervous system and smooth/striated
muscle balance. Any number of acute and chronic stress factors working via the sympathetic
end plate may be involved.
In a case study, Stanford developed protocol using myofascial trigger point assessment
and release therapy (MFRT) in conjunction with paradoxical relaxation therapy (PRT) was
applied on 138 men with CP/CPPS. Results showed effective therapeutic approach for the
management of CP/CPPS, providing pain and urinary symptom relief. A long term study with
meadian follow up 4.8 years further supports this line of management (Anderson et al, 2011).
Extracorporeal Shock Wave Thermotherapy (ESWT)
Zimmermann and coworkers have published an interesting outcome concerning the

effects of extracorporeal shock wave therapy (ESWT) in patients affected by chronic pelvic
pain syndrome; 60 patients had undergone low-energy-density ESWT with a perineal
approach without anaesthesia and compared them with a control group (placebo group). All
30 patients per group completed outpatient treatments and follow-ups without any problems
and without any drop-out (Zimmermann et al, 2009). Zimmermann and his group found that
this prospectively randomized, double-blind study is the first to reveal perineal ESWT as a
therapy option for CPPS with statistically significant effects in comparison to placebo.
Moreover, they concluded that ESWT may be interesting because of its easy and inexpensive
application, the lack of any side effects, and the potential for repetition of the treatment at any
time. However, there was doubt about statistical power of this study.
Future Prespectives
Central Role, Newer Markers, Genetics and Multi-Disciplinary Treatment
There are many new promising areas in which future research would be probably
rewarding:
Recent evolving aetiological model includes a peripheral initiating event in the

genetically anatomically/physiologically susceptible patient.
The role of the central nervous system in chronic pelvic pain is now appreciated. It is
believed patients with chronic pain as in CP/CPPS undergo measurable change in the
brain anatomy function due to repetitive painful stimuli over time. This can lead to
sensitization known as temporal summation of pain.
The biomarker discovery process in CP/CPPS has already begun and ingoing
continuous evolutions.
Promising results published by using UPOINT Classification system by considering
each patient as a unique individual and tailoring treatments to a specific patients
clinical phenotype would improve therapeutic outcomes. Most patients will be
categorized with more than 1 UPOINT domain and will require multimodal therapy.
Combining treatment trials with imaging studies, biomarker and genomic, in addition
to epidemiologic and symptom-based assessments, will maximize the ability to
identify disease etiology and pathogenesis, as well as achieve effective treatment.
Multidisciplinary team of urologists, internists, pain specialists, gastroenterologists,
rheumatologists, physical therapists, neurologists and primary care physicians should
co-operate in order to reach to optimal management of CP/CPPC.
Summary
CP/CPPS is still presenting true considerable challenge to urologists. Despite large scale
clinical trials and observational cohort studies have been conducted, more collaborative work
that involves biopsychosocial approach is warranted.
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Chapter VII
Management of Pelvic Pain:

What Is the Evidence?
Renato Seracchioli, Giulia Montanari,

Elisa Geraci and Stefania Alvisi
Minimally Invasive Gynecological Unit of the SantOrsola University Hospital of
Bologna, Italy
Introduction
Chronic pelvic pain (CPP) is a very common and complex condition. Most commonly
(but not accepted from all authors) CPP is defined as a non-cyclic pain of at least 6 months
duration localized to the anatomic pelvis, anterior abdominal wall at or below the umbilicus,
the lumbosacral area or the buttocks, which results in functional or psychological disability or
lead to medical care [1, 2]. A lack of physical finding and a normal examination dont
exclude the significance of a patients pain. In fact, pain is always subjective and its definition
avoids tying pain to the stimulus [1]. The criterion of 6 months is somewhat arbitrary; the
rational is that after several months of pelvic pain, the pain itself becomes an illness rather
than a manifestation of some other disease [3]. Possible temporal characteristics include pain
to be recurring or constant [4].
Fauconnier et al. defined CPP as a complaint including dysmenorrhea (cyclic pain), deep
dyspareunia (intermittent pain) and non-cyclic chronic pelvic pain, as a matter of fact women
with CPP often have these symptoms as part of their symptoms complex [5].
Prevalence of CPP is probably underestimated. This is in part due to the estimate that
only one third of women with CPP seek medical care [4] and this is on average after two to
five years suffering from it [6]. In studies of clinical populations, as up to 40% of women in a
large questionnaire survey reported not seeking any medical care for their pelvic pain [7].
CPP estimated prevalence ranges from 2.1 to 24% of the female population worldwide [8]
aged 15 to 73 years, which is similar to the prevalence of migraine, headaches, asthma and
174 Renato Seracchioli, Giulia Montanari, Elisa Geraci et al.
low back pain in woman [9, 10]. More frequently pelvic pain is diagnosed in young women;
the mean age of patients with CPP is about 30 years old [6].
Chronic pelvic pain is the main complaint of 10% of gynaecologic consultations [4],
leading to 17% hysterectomies [11] and more than 40% of gynaecologic diagnostic
laparoscopies [12].
Recent researches suggested that even if symptoms continued, many women became
dissatisfied with the care they received and refrain from seeking help [13]. Living with
chronic pelvic pain has a significant impact on patients quality of life. Both emotional and
sexual functioning are involved. Patients also report lower general physical health scores than
controls and they have a high incidence of comorbidity, sleep disturbance and fatigue [14].
Pelvic pain can lead to disability and suffering, possible employment loss, marital discord and
medical misadventures, so it can be considered as an important issue in the healthcare of
women [6, 15, 16].
Causes
CPP has many potential causes and many aetiologies can contribute to determine it.
Despite there are associations with specific pathological processes, conditions related to
pelvic pain are often unclear. In some cases no tissue damage or any pathophysiologic causes
are found [4] suggesting psychological basis of this condition [1, 16].
Potential sources of pelvic pain include the reproductive, genitourinary and
gastrointestinal tracts, but it can also origin from somatic sources like bones, ligaments,
muscles and fascia [1].
Frequently to determine CPP contribute several diagnoses (pain generator) [6] and
physical, functional and psychological etiologies can be overlapping making things more
complicated [17]. For example endometriosis, bowel irritable syndrome, poor posture and
emotional stresses can contribute to pain in a single patient needing a multidisciplinary
approach in the evaluation and treatment.
It may be useful to classify etiologies of pelvic pain into gynecological and non
gynecological disorders (interstitial cystis, irritable bowel syndrome, pelvic floor tension
myalgia and abdominal myofascial pain syndrome).
Gynecological causes of CPP include endometriosis, pelvic inflammatory disease,
adhesive disease, pelvic congestion syndrome, adenomyosis and leiomyomas.
Many women with CPP have more than one disease that might lead to pain and if more
than one organ system is involved pain usually referred greater. The most common diagnoses
are endometriosis, adhesions, irritable bowel syndrome and interstitial cystitis [18, 19, 20].
Endometriosis occurs in 71-87% of women with chronic pelvic pain in the general
population [21] and it is found in at least one-third of women who undergo laparoscopy to
evaluate CPP [12]. It can be considered the most prevalent diagnosis associated with pelvic
pain symptoms [18]. This association is also supported by the significant improvement in
CPP observed in patients who undergo surgical treatment for endometriosis [22].
Endometriosis associated pain starts as dysmenorrhea in 90-95% of women [23]
frequently associated with dyspareunia in deep vaginal penetration. These symptoms are
characteristic of endometriosis, but theyre not unique and they cannot justify themselves this
Management of Pelvic Pain: What Is the Evidence? 175
diagnosis. Diagnosis of endometriosis requires histological documentation of ectopic

endometrial glands and/or stroma proliferation [6]. However there is evidence that a clinical
diagnosis may be correct in up to 80% of cases and empiric treatment may be effective [24].
Based on visual survey at surgery and histological diagnosis, we can subdivide
endometriosis in three categories: superficial peritoneal endometriosis, deeply infiltrating
endometriosis (DIE) and ovarian endometriosis [25].
Even if is possible to find CPP in all the lesions types, the association with deep
infiltrating endometriosis is more frequent [26].
Relationship between endometriosis and pelvic pain is complex and not yet clear. As a
matter of fact endometriosis does not always cause pain and the severity of the disease does
not usually correlate with symptoms [27, 28]. Otherwise, after surgery pain may return
without lesion recurrence, suggesting that it could be due to activity in the central nervous
system (CNS) [29].
There are few hypotheses again about CNS engagement. Lesions may produce pain by
compressing or infiltrating nerves [30]. Another mechanism hypothized is the direct
innervation of ectopical endometrial growths by sensory and sympathetic fibers. It was shown
in a rat model and in womens lesions tissue resulting in communicatyion ways between the
growth and pain. [31, 32]. Mechsner et al [33] also found a correlation between nerve fiber
density and severity of pelvic pain or dysmenorrhea.
In clinical studies Fraser et al. demonstrated sensory, sympathetic and parasympathetic
fibers in different types of lesions, reporting a denser innervations in DIE than other lesion
types and particularly in rectal DIE lesions [34, 35]. This conclusion would be in accordance
with Fauconnier et al. that reported for the first time a correlation between chronic pelvic pain
and endometriosis and they also demonstrated that different type of pain are associated with
specific location of endometriosis foci. In particular they found a correlation between deep
dyspareunia and involvement of the uterus-sacral ligaments, painful defecation with vagina
lesions, gastrointestinal symptoms with bowel involvement and lower urinary tract symptoms
with bladder nodules. In their study they noticed that severe dysmenorrhea is correlated with
adhesions in the Douglas pouch. Moreover, they observed an higher rate of non-menstrual
CPP in patients with bowel DIE lesions which is supposed to be dependent on a sclerosis and
fibrotic reaction in the bowel wall that persist even when the endometriosis is no longer active
[5].
Even if there are many factors that influence pain experienced in women with
endometriosis, new researches suggested that a major contributing factor for pain is the
sensory and autonomic activity derived from nerves sprouted from nearby tissues to innervate
the ectopic growths. Ultimately this spreading seems to affect neuron activity in the spinal
cord and brain contributing to pain experience rather than the effect determined by the
endometriosis growths themselves [29].
Endometriosis together with pelvic inflammatory disease, bowel inflammatory disease,
prior abdominopelvic surgery and perforated appendix are known causes of pelvic adhesions
recognized themselves as contributors of chronic pelvic pain [6]. However, one-half of
women with adhesions have no history of these common etiologies [36].
The diagnosis of adhesions may be suspected by the presence of the exacerbation of pain
by sudden movements, intercourse or physical activities [6].
The relationship between adhesions and pelvic pain is controversial [36]. However, in a
meta-analysis of over 3000 women with CPP and 2000 controls, Saravelos et al. [37] showed
a major prevalence (36%) of adhesions in women with CPP compared to the control
group (15%).
Diagnosis
The evaluation of chronic pelvic pain is difficult because of the complex etiology and the
presence of associated disorders that need a general approach to the patient including a
thorough medical history. The correct approach to pelvic pain also requires a collection of
obstetrical and gynecological history and a physical examination, but also a screening for
gastrointestinal, urologic, musculoskeletal and neurological disorders. Psychological traits
and marital satisfaction, sexual history and behavior should also be evaluated [16].
The correct pattern in this diagnostic process is not clear; in effect no precise guidelines
exist to illustrate the patterns of diagnosis and subsequent specialist referral [16].
Obtaining a complete history is a crucial component of the clinical examination, a
systematic evaluation of pain should include: its severity and quality, presence of
precipitating or alleviating factors, associated symptoms or previous pain treatments and
presence of radiation of pain in other regions [16]. If pain is present, patients should mark on
a pain map the location of their pain to distinguish if it could have a visceral origin (described
as not well localized and depicted as fairly diffuse) or a somatic origin (usually reflects a
dermatomal distribution or a myotomal pattern) [6]. A cyclic pattern (menses related) pain
could be due to a gynecological disorder, but interstitial cystitis and irritable bowel syndrome
can also have this pattern.
A more complete evaluation of painful symptoms severity is possible using visual
analogue scales, numerical rating scales and verbal descriptor scales. The visual and the
patients rating scales have some limitations about their understanding and accuracy [21]. The
numerical scales have been proposed as the best candidates in most situations, but the
multidimensional verbal scale can be more detailed and a more sensitive instrument for the
relatively large number of alternative responses possible. The McGill Pain Questionnaire is a
multidimensional verbal scale with descriptive terms helping patients to define their own pain
[21]. The importance of health related quality of life questionnaires is to understand how the
pain affects daily living and sexual activities and personal relationships.
Intake pain questionnaires greatly facilitate the ability to obtain a detailed history, but
they cant replace patients story [16].
In our clinic we believe that obtaining a complete medical history is the first step to
create a relationship between patient and doctor and to highlight clinical elements to guide the
subsequent exams. Conversation starts with gynecological and obstetrical history. Then we
usually analyze symptoms like dysmenhorrea, dyspareunia and chronic pelvic pain, asking
patients to grade the presence and severity of pain by using a 10-point visual analogue point
visual analogue scale (VAS) [38]. Complementary information are the presence of recurrent
genitourinary infection, abnormal bleedings and headache or stress association. To detect
bowel function women have to define their defecation frequency, to describe if there is pain
or bleeding during defecation. To detect urinary dysfunction women are asked to score their
symptoms of dysuria, if it is present. Its important to ask women specific questions about
bowel, bladder and sexual functions considering their possible reluctance to talk about them
[6]. To assess the impact of pelvic problems on sexual desire, frequency, satisfaction, orgasm
and discomfort we use Sexual Health Outcomes in Women Questionnaire (SHOW-Q) [39].
The impact of pathology in womens health related quality of life is examined using the Short
Form 36 health survey (SF-36), a validated multi-purpose health survey with 36 questions
[40].
Physical examination is often painful or emotionally and physically stressful for many
women with pelvic pain but in our experience its a key exam in the evaluation of women
with CPP. Physical examination should aim to detect the exact anatomic location of
tenderness eventually attempt to define it duplicating the pain by palpation or positioning
[36].
Based on clinical findings, we prescribe subsequently instrumental exams (laboratory and
imaging) [6]. Pelvic ultrasonography is a routine procedure. Ultrasound is readily avaible,
relatively inexpensive and does not expose the patient to radiation, but it can be considered a
subjective exam because of its operators dependence. In our clinic, transvaginal
ultrasonography is performed by ultrasonographers with a long experience in endometriosis
and chronic pelvic pain. Transvaginal and transabdominal ultrasound (TVUS and TAUS) are
very accurate modalities to evaluate the female genital tract [41]. In CPP the ultrasound
trasducer can also identify points of maximal tenderness which can be very useful in the
diagnosis. However, the efficacy of ultrasonography for the assessment of women with CPP
has not been widely evaluated [42].
Several studies confirmed the high sensitivity and specificity of TVUS in the diagnosis of
ovarian endometrioma [43-48] but there is doubt regarding peritoneal endometriosis detection
[49]. The evaluation of soft markers like ovarian mobility and specific tenderness can have
a role to study women with CPP. Ultrasound findings are important to avoid laparoscopy in
patients with CPP: a normal scan based on the absence of hard and soft markers may exclude
a significant pelvic pathology [42]. Sometimes, may be necessary to associate TVUS with
other methodology like bloody markers monitoring, abdomen ultrasound, urography
cistoscopy, etc.
Computer tomography can provide important information on involvement of the
gastrointestinal tract [50]. Magnetic resonance imaging (MRI) is usefull in characterizing
pelvic masses as well as diagnosing adenomyosis, endometrioma, or deep endometriosis, but
its use is limited by high cost and varying avaibility [41].
When a structural cause has been excluded, a neurological-psychological opinion is often
requires [51].
The diagnosis is often determined by exclusion of other diseases. In some cases a
diagnostic laparoscopic surgery is required and it is probably the most useful invasive
investigation [16]. However the proportion of non-diagnostic laparoscopy is high [36], so a
thorough clinical assessment is fundamental and it may lead to avoid the unnecessary surgical
procedures [41].
Published series of laparoscopies for CPP suggest that endometriosis is diagnosed in
33%, adhesive disease in 24%, but in 35% of laparoscopies there is no evidence of pelvic
pathology [12]. These findings suggest that the major role of laparoscopy is to diagnose
endometriosis and adhesions in which its the gold standard [41].
In endometriosis, laparoscopy takes an important place because of the needing to perform
a thorough and complete inspection of the pelvic cavity and to allow diagnosis with lesions'
biopsy. Laparoscopic evaluation requires the visualization of all of the common sites of
endometriosis [36] and it is very important too in women with chronic pelvic pain to fully
describe the appearance, depth of infiltration, size and distribution of endometriotic lesions
[36]. In our clinic (in accordance with Howard's study [36]) we used to take photographs and
videotapes to document findings because we think it's a very helpful procedure to
impair patients' consciousness about their pathology, with the possibility to use it as material
of study.
Treatment
Treatment of chronic pelvic pain, as related by F. Howard, may consist of two
approaches: treating chronic pain itself as a diagnosis or treating the diseases or disorders that
might be its causes or contributor factors. These two approaches are not mutually exclusive
and in many patients effective therapy is best achieved by using both [52]. This way can be
helpful for an optimal pain management.
Non Specific and Global Treatments

When a specific diagnosis is not possible or when the target treatment is failed, it is
suggested to move toward non specific and global interventions for pain relief.
Pharmaceutical Approach
Analgesics are the mainstay of treatment of CPP and include peripherally acting and
central acting agents. Those that act primarily peripherally include non steroidal anti-
inflammatory drugs (NSAIDs), acetominophen and aspirin. Those that target primarily central
mechanism are represented by the opioid class of medications [4].
Kroenke et al. provided an evidence-based approach to the pharmacotherapy of chronic
pain in which they consider the NSAIDs the first-line treatment [53].
OMalley et al. performed a trial in which they demonstrated how antidepressants can be
effective for various physical symptoms [54]. In particular, tricyclic antidepressants (TCAs)
have the longest clinical record in the antidepressant class for the treatment of pain
conditions. Recent studies instead demonstrated conflicting results regarding another class of
antidepressants, the selective serotonin reuptake inhibitors (SSRIs) in the treatment of pain
[4].
Finally, Baiwa et al. showed how antidepressants are most commonly used in the context
of multimodal treatment for pain and comorbidities such as depression or anxiety [55].
Anticonvulsivants, as gabapentin, also show some good results on pain relief, considering
that neuropathic pain is sometimes the cause of CPP [56].
Sator et al. demonstrated how gabapentin alone or in combination with amitriptyline is
better than amitriptyline alone in the treatment of chronic pelvic pain [57].
Neuroablative and Neurolytic Approach
Neuroablative therapy is more often used for specific nerve disfunction, but sometimes it
may reduce CPP too. It includes surgical transection or excision of specific nerves (especially
presacral neurectomy that consists in the excision of the superior hypogastric plexus),
injection of neurotoxic chemicals (alcohol, phenol or hypertonic) or use of energy like
cryoablation or thermocoagulation [36].
Psychological Approach
Hypothesizing psychogenic nature and psychological aspects associated with organic

etiology, we can consider a multidisciplinary approach. It includes forms like counseling,
group therapy, cognitive behavioral therapy and biofeedback.
Turk et al. reported that cognitive-behavioural therapy alone or within the context of an
interdisciplinary pain rehabilitation program has the greatest empirical evidence for success
[58]. Haugstad et al. also described an improvement of psychologic distress, pain experience
and motor functions after a somatocognitive therapy combined [59].
Finally, Howard confirmed that, although this intervention may be limited by cost or
patients compliance or acceptance, psychological treatment may decrease suffering and
disability in CPP patients [36].
Disease Specific Treatments

When a specific diagnosis is possible, the therapy can be target to treat it.
Endometriosis Therapy
Treatment of endometriosis associated pain is complex and none of the option are ideal
for all patients; clinicians should considered patient's age, reproductive plans, presence of
infertility, pain severity and attitude toward surgery or hormonal medications to design a
treatment plan [6].
Medical therapy is able to treat the symptoms and to modify the course of the disease. It
may include Oral Contraceptive Pills (OCP), Gonadotropin-Releasing Hormone (Gn-RH)
agonist and progestogens.
Its a common opinion that OCP can be considered a good pharmacological choice as
they are safe, well tolerated, relatively inexpensive and they can be administered for long
periods [60]. Now oral contraceptives are a long standing approach and a cyclical or
continuous regimen is possible according to patient preferences [6, 61].
OCP inhibit ovarian function and induce a pseudopregnancy state which produce
decidualization of endometrial tissue and impairment of endometriosis related-pain by
menstrual bleeding reduction [26].
There is general agreement that conservative surgery by laparoscopy is the treatment of

choice in both ovarian and deep endometriosis [4, 62, 63, 64, 65], especially when they are
accompanied by severe alteration of pelvic anatomy with organ dysfunction and/or quality of
life impairment [66].
Laparoscopic surgery can significantly reduce painful symptoms and improve quality of
life in 67-80% of endometriosis patients [22]. Jacobson et al. also demonstrated a significant
pain relief six months after surgery for minimal, mild and moderate endometriosis [67].
However, it is generally accepted that surgical outcomes are highly operator-dependent and
optimal results can be assured in tertiary care and referral centre, where is possible a
multidisciplinary approach and advanced surgery [68, 69]. In our clinic, referral centre for
endometriosis and pelvic pain, each case is discussed from an expert team to define the most
correct approach to the patient. After surgery, patients are submitted to a follow-up to observe
symptoms pattern, quality of life level and to prevent recurrence. It has been demonstrated in
many studies that surgery is possible to be followed by recurrence of endometriotic implants
and painful symptoms [61, 70]. Long term OCP therapy can be a reliable adjuvant post-
operative measure to prevent or reduce frequency and severity of recurrent dysmenorrhoea
and anatomical relapse of endometriosis [61, 71].
Diet modification is studied as a specific therapy for endometriosis, but there are only
few evidences about it. Recent studies have considered diet as a factor that could influence
endometriosis's pathogenesis, symptoms and recurrence after surgery [72, 73].
Pelvic Adhesions Disease
Despite the frequency of finding pelvic adhesions during surgical treatment, there are
many disputes and limited studies about their treatment. There is no consensus on the
outcome of adhesiolysis in patients with CPP [74].
Peters et al. in a randomized trial [75] about adhesiolysis, found no pain symptoms
improvement in women who underwent adhesiolysis by laparotomy compared to a control
group, except in patients with severe adhesions [75]. This is in accordance with Cheong et al.
that in their study concluded: there is not evidence of benefit rather than evidence of no
benefit [76]. Even if surgery itself is a recognized causes of adhesions [77], compared to
traditional laparotomy, laparoscopy technique has many advantages, even just a lower
incidence of adhesions [78] so it is now generally accepted as preferential approach.
In our experience, adhesiolysis is not recommended as the operation itself, but it may be
indicated during laparoscopic time if they are visible. As for deep endometriosis, laparoscopic
lysis of adhesions seems to be safe in the hands of well-trained laparoscopic surgeons [79].
Conclusion
The successful treatment of women with CPP often requires a multidimensional approach
given the context of a complex overlap of possible etiologies. It is important to assess the
cause of CPP in order to be able to choose the most appropriate therapeutic approach,
according to the needs of women. However, when is not possible to find the cause, it is
important to establish a non specific therapy. Typically, a combination of approaches yields

the greatest symptomatic improvement.
Treatment must be individualized, taking the clinical problem in its entirety into account,
including the impact of the disease and the effect of its treatment on quality of life.
Finally, we do not have to forget that this kind of pain is chronic, so it is important to
ensure these patients a point of reference that provides an appropriate follow-up and
eventually solutions for any problems or a confirmation about the success of therapy. It is also
important to involve the woman in all decisions, to be flexible in diagnostic and therapeutic
thinking, to maintain a good relationship with the woman and to seek advice where
appropriate from more experienced colleagues.
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[66] Roman H; Vassilieff M; Gourcerol G; Savoye G; Leroi AM; Marpeau L; Michot F;

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pelvic pain associated with endometriosis. Cochrane Database Syst Rev, 2009; 7(4).
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of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod
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[69] Royal College of Obstetricians and Gynaecologists. The investigation and management
of endometriosis. Green-top Guideline No.24 2006.
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Recurrence of ovarian endometrioma after laparoscopic excision. Am J Obstet Gynecol,
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oral contraceptive pills and postoperative pain management after laparoscopic excision
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71.
[72] Zeyneloglu HB; Arici A; Olive DL. Environmental toxins and endometriosis. Obstet
Gynecol Clin North Am, 1997; 24(2), 307-29.
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49(4), 698-703.
[74] Vercellini P; De Giorgi O; Pisacreta A; Pesole AP; Vicentini S; Crosignani PG.
Surgical management of endometriosis. Baillieres Best Pract Res Clin Obstet Gynaecol,
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[76] Cheong Y; William Stones R. Chronic pelvic pain: aetiology and therapy. Best Pract
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Chapter VIII
Physical Therapy in Management of

Women with Chronic Pelvic Pain
Mary Lourdes Lima de Souza Montenegro*

Department of Gynecology and Obstetrics,
School of Medicine of Ribeirao Preto- University of So Paulo, Brazil
Abstract
Chronic pelvic pain (CPP) is defined as non-menstrual or noncyclic pelvic pain with
duration of at least 6 months, sufficiently intense to interfere with habitual activities and
requiring clinical or surgical treatment. There are great difficulties in establishing the
primary cause of CPP and consequently in proposing adequate treatment, because there is
a complex interaction between the gastrointestinal, urinary, gynecologic,
musculoskeletal, neurologic and endocrine systems, also influenced by psychological and
social factors. The estimated prevalence of CPP is about 3.8% among women aged 1573
years, ranging from 14 to 24% among women of reproductive age, with a direct impact
on their marital, social and professional life. About 60% of women with the disease never
receive a specific diagnosis and 20% are never submitted to any investigation to elucidate
the cause of the pain. Although the more common diagnoses in women with CPP are
endometriosis, adhesions, irritable bowel syndrome and interstitial cystitis. The
involvement of the musculoskeletal system in the genesis and perpetuation of CPP has
been increasingly demonstrated particularly the abdominal myofascial pain syndrome and
tenderness of pelvic floor muscles, showing a crescent necessity of multidisciplinary care
involving gynecologists, physiotherapists, psychologists, etc. to manage women with
CPP. So, in this chapter we will discuss about the physical therapy in management of
women with chronic pelvic pain
* Corresponding author: Mary Montenegro, Address: Av Bandeirantes, 3900 - 8andar, ZIP 14049-900, Ribeirao
Preto - Sao Paulo, Brazil, Tel.: +551636025110; fax +551636330946, E-mail: montenegromlls@gmail.com.
188 Mary Lourdes Lima de Souza Montenegro
Concern
Chronic pelvic pain (CPP) is defined as non-menstrual or non-cyclic pelvic pain with a
duration of at least 6 months, sufficiently intense to interfere with habitual activities and
requiring clinical or surgical treatment [1]. There are great difficulties in establishing the
primary cause of CPP and consequently in proposing adequate treatment. At the time of
diagnosis, we frequently face a complex interaction between the gastrointestinal, urinary,
gynaecological, musculoskeletal, neurological and endocrine systems, also influenced by
psychological factors [2] such as depression, hypochondria and somatisation, in addition to
sociocultural factors including physical and sexual violence [3]. The estimated prevalence of
CPP is 3.8% among women aged 1573 years, ranging from 14% to 24% among women of
reproductive age, with a direct impact on their marital, social and professional life (47).
About 60% of women with the disease never receive a specific diagnosis and 20% never
undergo any investigation to elucidate the cause of the pain [4]. Thirty-nine per cent of the
women seen at primary care units complain of pelvic pain, which accounts for 4050% of
gynecological laparoscopies, 10% of gynecological visits and approximately 12% of
hysterectomies [5-7]. Additionally, CPP involves direct and indirect costs exceeding 40
billion dollars a year in the USA [8]. No studies have been able to identify risk factors for the
disease, a fact explained in part by the characteristics of the epidemiological data of each
locality and by the difficult access to the information of the studies. A systematic review
concluded that drug or alcohol abuse, abortion, increased menstrual flow, pelvic inflammatory
disease, pelvic pathology, caesarian sections and psychological comorbidities are associated
with the disease [9, 10]. Despite of this, the more common diagnoses in women with CPP are
endometriosis, adhesions, irritable bowel syndrome and interstitial cystitis, the involvement
of the musculoskeletal system in the genesis and perpetuation of CPP has been increasingly
demonstrated [11] nevertheless few studies about musculoskeletal system and CPP in women
are available.
Musculoskeletal System and

Chronic Pelvic Pain
The involvement of the musculoskeletal system in the genesis and perpetuation of
chronic pelvic pain (CPP) is being increasingly demonstrated at the last years [11]. There are
strong evidences that up to 85% of patients with CPP present dysfunction of the
musculoskeletal system, including postural changes such as lumbar lordosis, knee
hyperextension and pelvis anteriorisation, as well abdominal myofascial pain syndrome and
spasm of the levator ani muscle and piriform syndrome [12, 13]. These dysfunctions can lead
to the adoption of abnormal postures [14] that contribute to increased tension and spasm,
consequently adaptive muscle shortening that exacerbate or perpetuate the pain [11, 13].
However, it has not been well established if musculoskeletal dysfunctions are a cause or a
consequence of CPP.
Physical Therapy in Management of Women with Chronic Pelvic Pain 189
Posture and Chronic Pelvic Pain

A widely accepted concept is that in the presence of a painful stimulus, the first muscle
reaction is increased of tension that may progress to a spasm and consequently to adaptive
shortening [15]. Thus, an early detection of muscle changes is essential and a musculoskeletal
evaluation is very important for the management of patients with CPP. Therefore, in the
evaluation of women with CPP, a special attention should be paid to the way of walk, facial
pain characteristics and antalgic postures [3, 16, 17]. Head alignment, shoulder positioning
and symmetry Tales triangle (distance between the medial epicondyle and the trunk),
curvature of the spine, pelvis and lower limbs should be analyzed in the evaluation of postural
deviations. It is also very important to evaluate the degree of shortening posterior chain
muscles by the measurement of the fingerfloor distance and the measurement of lower limb
length, i.e. both the real measurement (distance from the anterosuperior iliac spine to the
medial malleolus) and the apparent one (distance from the umbilical scar to the medial
malleolus) [18, 19]. These measurements should be made to determine the occurrence of
possible pelvic drops or involvement of the posterior muscle chain caused by inadequate
posture. Although these changes may not be the primary cause of the clinical condition, they
can contribute significantly to the worsening of pain and tension. In addition, postural
examination can be assessed in a strictly clinical manner, with the examiners recording the
static posture adopted by the women. Because of its simplicity this type of evaluation can be
incorporated into the clinical practice of evaluation of women with CPP, minimizing factors
that may worsen or perpetuate CPP and being of help regarding the referral of these women to
specialized services.
Abdominal Myofascial Pain Syndrome

and Chronic Pelvic Pain
The abdominal myofascial pain syndrome (AMPS) is one of the most common causes of
CPP and is characterized as intense and profound pain in the abdominal region originating
from myofascial triggering points (MTrP) [20]. These MTrP, in turn, are hyperirritable points
usually localized within a skeletal muscle fascia or in the muscle covering fascia, and can be
classified as active or latent [21]. Active MTrP can cause pain at rest and produce referred
pain similar to that felt during compression of the point. In contrast, latent MTrP do not cause
spontaneous pain but may limit movements and cause muscle weakness. Latent MTrP may
become painful when direct pressure is applied to them. In addition to painful phenomena,
MTrP can also produce muscle spasms and autonomic phenomena such as piloerection,
vasoconstriction, hyperhydrosis, changes in temperature, and a variety of somatovisceral
reflexes [21, 22]. AMPS usually affects women more than men (54% versus 45%), and is
more frequent among women aged 3040 years [23]. The estimated prevalence is about 30%
in primary medical care centers and 8593% in centers specializing in the treatment of pain
[21]. In our experience, about 30% of women with CPP attended by our group had AMPS.
Physiopathology of Abdominal Myofascial Pain

Syndrome
Different physiopathological mechanisms have been proposed to clarify the development
of AMP. Endplate noise in MTrP [24] and connections between an MTrP and the spinal cord
have been described. Despite lack of scientific evidence, some factors are known to
precipitate and perpetuate AMPS. Among them, we may mention muscle wasting, muscle
ischemia, visceral pain referral, radiculopathic compression of motor nerves, climatic causes,
anxiety [25], macrotraumas due to tension or contusions, microtraumas due to repetitive
muscle use leading to fatigue and to the gradual beginning of AMPS, mechanical factors such
as inadequate posture, scoliosis and lack of ergonomic adequacy during work, degeneration
caused by aging leading to structural degradation of bones and joints with a gradual loss of
myofascial flexibility, endocrine and metabolic deficiencies such as insufficiency of thyroid
hormones and estrogen, nutritional vitamin and mineral deficiencies, and viral and parasitic
infections [26, 27]. The precise mechanism of generation and perpetuation of MTrP is
unknown but the facilitated release of acetylcholine in motor endplates with the release of
vascular and neuronal substances is believed to result in depolarization and consequently in
sustained muscle fiber contraction [27]. This sustained contraction results in localized
ischemia that causes the release of neurokinins, histamine, serotonin and prostaglandins that
stimulate the nociceptors, increasing acetylcholine release. This generates reflex muscle
contraction resulting in a sustained cycle of muscle pain and spasm. Another explanation
would be that the transitory load on a muscle may injure the sarcoplasmic reticulum and, with
an impaired T-tubule system, the stored calcium ions are released and taken up again in the
injured area, causing permanent fiber contraction [28].
Abdominal Wall Evaluation

There is no gold standard criterion for the diagnosis of AMPS, but palpation is the
method most extensively used [29]. Initially, Carnetts sign is a simple maneuver that
discriminates between parietal and visceral pain. With the physicians placing a finger on the
abdominal wall, the patient is asked to stretch and slowly raise her legs, neck or shoulders and
to contract her abdominal rectus muscle [30]. Pain of myofascial origin is aggravated by the
exerted pressure. The criteria most often used for the diagnosis of AMPS are: presence of a
hypertonic point in a set of muscle fibers (taut band/tender point), the patient feeling pain
when the point is palpated, a referred pain pattern, muscle contraction as a local response to
palpation of the point (local twitch response), and limited movement amplitude [23]. In this
way, it is crucial that the physician differentiates tender from trigger points that refer to two
separate and distinct anatomical entities. The differential diagnosis was explained in detail by
Schneider [31]. To accurately feel and locate the taut bands it is important to perform
effective palpation of the muscles and of their fasciae, a procedure that can be executed in
two ways: flat palpation applied with the ventral surface of the finger for an initial
determination of muscle tonus or spasm, and finger tip palpation for the detection of taut
bands and MTrP through the muscle fibers [27]. The abdominal wall muscles to be examined
are the external and the internal oblique. For the examination the patient should lie down in
the supine position and relax to allow the examiner to evaluate her abdominal wall while
searching for tense musculature [21]. During the evaluation the patient should perform
diaphragmatic breathing in order to stretch her muscles in a passive manner and increase their
sensitivity to palpation [20]. When the examiner finds a TrPM and presses it, the patient may
respond in different ways, ranging from a light jump from the gurney to crying, but the most
frequent response is the jump sign. Autonomic symptoms may also occur, and compression of
an MTrP may result in ipsilateral or contralateral referred pain [22].
Complementary Examinations
Algometry
Algometry has been used for the evaluation of sensitivity to pain and the assessment of
pressure perception [32]. The algometer can perform the pressure threshold measurement
(PTM), which is defined as the minimal pressure that causes pain or discomfort in tender
spots [33]. The value of PTM for clinical evaluation of soft tissue pathology has been
reported by several investigators, and the reliability of the method for identifying MTrP and
qualifying pain sensitivity has been documented [34] Clinically, the PTM gauge can be used
as a semi-quantitative method for the measurement of intensity of tenderness, location of
tender spots, to prove to the patient that tenderness, pain, MTrP and their sensitivity correlate,
for long-term follow-up of change in pain, and evaluation of activity in inflamed joints. In
addition, it is used for medico-legal documentation since the reproducibility of pressure
threshold indicates that the records of pain intensity are quantitative and objective [33]. PTM
has some limitations, such as the variability in pain perception between and within
individuals at different times. Depression, anxiety and tension may affect the results and
therefore the measurements should be made with the muscle at rest, Excessive pressure on the
MTrP may alter the examination, and examination of points located in deep muscles or in the
presence of excess adipose tissue may not be precise.
Ultrasonography
Ultrasonography is utilized to perform differential diagnosis with other conditions,

including hernia and wall endometriomas. This procedure permits the evaluation of the local
contractile response of tense band fibers in an MTrP, and has great potential as an imaging
technique for the diagnosis of AMPS, which can be widely used to determine the presence of
MTrP in an objective manner [20].
Treatment
In general, the treatment of AMPS requires a multidisciplinary approach in order to
interrupt the pain cycle, to abolish the MTrP and to restore muscle flexibility, eliminating the
factors predisposing to and perpetuating pain [27]. The majority of information about
treatment refers to regional myofascial pain syndromes but not the abdominal one.
Pharmacologic Treatment
Includes analgesics and medications to induce sleep and relax muscles. Antidepressants,
neuroleptics, or nonsteroidal nti-inflammatory drugs are also often prescribed [22].
Needling
Two types of needle are commonly used: hypodermic and acupuncture. Hypodermic
needles allow needling with infiltration of a local anesthetic during the procedure. The local
anesthetic helps to relieve post-needling soreness. Acupuncture needles are stainless steel
filiform needles with a diameter range of 0.250.35 mm. They are finer and less traumatic.
However, they do not permit infiltration of a local anesthetic during the procedure. One of the
aims of needling is to mechanically break up the MTrP. Contraindications to needling include
bleeding diathesis, anticoagulation, local or systemic infection and inability to rest the treated
region after the procedure [27].
Trigger Point Injections
MTrP injection may be performed using short-acting, long acting, or a combination of

local anesthetics. A 50:50 mixture of 1% lidocaine and 0.25% bupivacaine is usually
employed [35]. Nevertheless, different anesthetics seem to have to be equally effective for
trigger point infiltration [36]. The question of how frequent, and over what duration, MTrP
injections should be tried is not always clear [21]. The use of MTrP injections also has some
contraindications such as anticoagulation or bleeding disorders, aspirin ingestion within three
days of injection, the presence of local or systemic infection, allergy to anesthetic agents,
acute muscle trauma, and extreme fear of needles [22]. MTrP injections may also cause
complications such as vasovagal syncope, skin infection, and pneumothorax. Needle breakage
is avoided by never inserting the needle to its hub and hematoma formation is avoided by
applying direct pressure for at least 2 min after injection [21, 22].
Manual Therapy (Ischemic Compression)
This therapy consists of applying sustained pressure to the MTrP sufficient to cause
moderate local pain that invokes the referred pain pattern; if very strong pressure is applied,
the local pain can overshadow the referred pain. Pressure should be applied for 3090 s or
until the patient reports improvement of symptoms and after a few seconds the procedure
should be restarted [22]. Ischemic compression has proved to be effective in the treatment of
fibromyalgia, since the ischemia produced modifies the circulatory perfusion of the skin,
permitting better oxygenation and nutrition at the MTrP site [37]. This therapy also has the
advantage of being noninvasive and inexpensive and of not increasing patient anxiety.
However, although it is a therapy of easy application, if performed in an inappropriate
manner, e.g. without appropriate analgesia, it may exacerbate and perpetuate pain.
Pelvic Floor Muscles and Chronic Pelvic Pain

Involvement of the pelvic muscles may be directly or indirectly related to the
development of CPP. Directly because a muscle trauma caused, for example, by pelvic
surgery may result in the development of a spasm and consequent adaptive muscle shortening
[13] and indirectly because the pain, when becoming chronic, may lead to the occurrence of
viscerovisceral or visceromuscular reflexes (as mentioned earlier), affecting the structures that
share the same nervous segmentation. This is probably what occurs in interstitial cystitis
which is associated with painful spasms of the pelvic floor muscles, complicating and
perpetuating the painful situation. The involvement of these muscles, which may explain the
high prevalence of dyspareunia (a frequent complaint among patients even in the absence of
disease of the abdominalpelvic cavity), may be a primary event and not simply a
consequence of CPP [15]. Few studies are available about the changes in the pelvic
musculature of women with CPP or about methods for the evaluation of these muscles.
Despite these limitations, some authors have stated that the muscles most affected in CPP are
the levator ani, the piriform and the internal obturator. Despite the effort invested in the
development of less subjective and more reproducible methods for the evaluation of pelvic
muscles, the digital examination carried out by vaginal palpation currently is the most reliable
method for the evaluation of these muscles [11, 12, 38-43]. The contraction of pelvic floor
muscles should be evaluated without performing the Valsalva manoeuver or using abdominal,
gluteal or hip adductor muscles, factors that might interfere with the evaluation [44-47].
Regarding the precision and reliability of methods for the evaluation of the pelvic diaphragm,
some studies have demonstrated that vaginal palpation with one finger currently represents
the most reliable method for the evaluation of these muscles as long as the patient is properly
instructed and the examination is performed by a qualified professional [48, 49]. During
palpation, a trained professional can distinguish the contractions generated by muscles of the
pelvic diaphragm from those generated by other muscle groups such as the abdominal, gluteal
and hip adductor muscles [48].
Pelvic Floor Muscles Evaluation

Pelvic examination should be performed in the most comfortable and delicate manner
possible as the pain sensitivity of these patients is often exacerbated. The bladder should be
empty and the examination should be started by inspecting the external genitals (vulva,
vestibule and urethra) for the detection of injuries or painful points, followed by the
traditional specular examination. Uni-digital vaginal examination must be performed next for
the evaluation of the urethra, base of the bladder and trigone region on the anterior vaginal
wall. Additionally, the uni-digital evaluation of pelvic floor muscles (levator ani,
pubococcygeal, puborectal, piriform and internal obturator muscles) must be performed [13].
Many patients have painful spasms of pelvic floor muscles [43]. This dysfunction may be
primary or secondary to other diseases such as interstitial cystitis and endometriosis. In
evaluation with both hands, special attention should be paid, if possible, to the presence of
irregularities, nodules and painful points in the vaginal fundus and in uterine-sacral ligaments
that may suggest the presence of pelvic endometriosis [50]. Before performing the combined
pelvicabdominal examination, it is necessary to block eventual triggering points in the
abdomen with analgesics. Rectal examination should be performed when necessary and in
these cases the rectovaginal septum should be carefully evaluated to determine the presence
of painful nodulations suggestive of endometriosis. Very intense discomfort upon rectal touch
may also be associated with irritable bowel syndrome. The intensity of dyspareunia shoud be
classified as absent (absence of pain during the sexual relation), mild (tolerable pain, does not
lead to the interruption of the sexual relation), moderate (intense pain sufficient to lead to the
interruption of the sexual relation) and intense (pain that hinders the sexual relation)
according to the limitation of sexual activity [50]. The tenderness of pelvic floor muscles
shoud be scored according to subject reactions: 0- no pain, 1- painful discomfort, 2- intense
pain. For a better discrimination between the muscles and other soft tissues, the subjects were
examined in the lithotomy position, as suggested by several authors [20-22].
Treatment
Chronic pelvic pain because by spasm of the pelvic floor muscles can be treated by
several modalities [39, 42, 51, 52] Local anesthetic blockade are associated with a success
rate of 72%. Another technique which is being increasingly studied is the injection of type A
botulin toxin into the affected muscles of the pelvic floor. This neurotoxin acts selectively on
the ending of the cholinergic peripheral nerves, inhibiting the presynaptic release of
acetylcholine, provoking a reversible chemical denervation and consequently leading to distal
axonal degeneration of prolonged, although transitory, action on the function of the motor
plate, reducing excessive tonic or phasic muscle activity, and thus increasing active and
passive motility with greater muscle lengthening [53, 54]. Electrotherapy are other
possibilities of treatment, in turn, transvaginal electrostimulation has been associated with a
success rate of 50%, approximately. Electrogalvanic stimulation has also been associated with
significant success rate. Intermittent percutaneous posterior tibial nerve stimulation has also
showed satisfactory preliminary results: subjective response in 42% of the patients, being that
21% remained [55]. However, long-term follow-up studies are needed to confirm the efficacy
of this procedure. On the other hand, transvaginal massage using the modified Thiele
technique, (massage from origin to insertion along the direction of the muscle fibres with an
amount of pressure tolerable to the subject) is showing greats results in our practice. We used
to apply Thiele massage over a period of 5 minutes once a week for 4 weeks [56] and our
results are very promising once the women had a great improvement during treatment and
after one, three and six months of follow-up. However is important to point out that the
choice of these adequate therapeutic resources depends on a detailed evaluation and on a
close interaction between gynecologists and physiotherapists that will permit the precise
identification of affected structures and the institution of the most appropriate treatment for
the needs of each patient.
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Chapter IX
Pelvic Morphology: Its Role in the

Differential Causes of Pelvic Pain
Rajesh Rout1 and Colin Nnadi2

1
Nuffield Department of Orthopaedics,
Rheumatology and Musculoskeletal Sciences, University of Oxford
2
Nuffield Orthopaedic Centre and John Radcliffe Hospitals, Oxford, United Kingdom
Abstract
Pelvic morphology plays a significant role in the Spino-pelvic relationship. Its
character influences the alignment of the spine in the lateral plane. Normally the head of
an individual is centred over the pelvis in the frontal and lateral planes. In certain cases
this does not always occur. When this happens in the lateral plane it is described as a
sagittal plane deformity. This condition involves a misappropriation of spinal alignment
and pelvic morphology characterized by compensatory mechanisms which manifest as a
painful deformity of the back. The patient will often describe pain located anywhere from
the top to the bottom of the spine including the pelvis. This problem is being investigated
and treated ever more frequently.
There are many causes of sagittal plane deformity (SPD): Trauma, degenerative
disease, inflammatory conditions, infection and tumour. Advancing age is commonly
associated with SPD otherwise described as the forward stoop of old age.
Pelvic morphology is described in terms of three main parameters: the pelvic
incidence (PI), the pelvic tilt (PT) and the sacral slope (SS). Pelvic Incidence is static
after skeletal maturity. Pelvic tilt and sacral slope are adjustable parameters. There is a
geometric relationship between these parameters in which PI = PT+ SS. Pathological
changes can be quantified using these parameters; ultimately it is these changes that will
contribute to a patients symptoms.
Within a normal range each of these parameters is unique to the individual person.
The ability to tolerate any pathological or physiological changes in spinal alignment
depends on the amount of compensatory reserve available within the confines of these
pelvic parameters.
200 Rajesh Rout and Colin Nnadi
In recent years, our understanding of the different constituent parameters has

increased greatly, and this article will aim to shed more light on what is a rapidly
evolving field.
Introduction
Sagittal plane deformity (SPD) is being investigated and treated ever more commonly by
spinal surgeons. Patients are presenting ever more frequently with this deformity and
symptoms of pain and a debilitating stoop. The relationship between the spine and the pelvis
are key in their contribution to sagittal balance. In the past, regional features of thoracic
kyphosis and lumbar lordosis have been used to assess spinal deformity, however it is the
global parameters (those that relate the alignment of the spine to a reference point on the
sacrum and pelvis) that have become more increasingly used in the assessment of SPD (1-3).
This article reviews the basics of the spino-pelvic relationship as well as the patients,
their investigation and treatment options.
Anatomy and Relationships

In order to understand the relationship between the spine and pelvis, an understanding of
their anatomy is required. The pelvis is formed from the ilium, ischium and pubis (Figure 1).
These three bones join in the acetabulum making the tri-radiate cartilage; they fuse during
puberty. Anteriorly, they are attached at the pubic symphysis, a secondary cartilaginous joint
(an immobile, fibrocartilaginous joint). Posteriorly, the pelvis is attached, via the sacroiliac
(SI) joints, to the sacrum and thus the axial skeleton. The SI joints have stability conferred by
intrinsic and extrinsic ligaments, and normally allow only small amounts of movement
ranging from about 3 to 17mm (4, 5).
The spine consists of 24 individual vertebrae: 7 cervical, 12 thoracic and 5 lumbar. In
addition the sacrum is usually formed from 5 fused vertebrae, and the coccyx from 4. In the
coronal plane, the vertebrae are aligned vertically, however, in the sagittal plane there are
lordotic curves of the cervical and lumbar vertebrae, and a kyphotic curve of the thoracic
vertebrae. In a normal population these values can vary quite widely (asymptomatic subjects)
(6-10). Values here are ranges from Kuntzs systematic review (kyphsosis is postive and
lordosis negative and values are 2 standard deviations) : cervical lordosis -17 28,
thoracic kyphosis +41 to 22, lumbar lordosis -44 22 (7). Cervical lordosis is usually
measured from the end plates of C2-C7, thoracic kyphosis from the end plate of T5 to T12
(cranial to this, the scapulae tend to obscure the image) and lumbar lordosis is usually
measured from L1 to L5 (7).
Despite the wide range of values above for each component of an individuals spine,
there is a much narrower range for overall alignment. Overall, the global sagittal alignment
can be assessed using the C7 Plumb line. This is a vertical line extended downwards from the
vertebral body of C7. It should intersect the sacral end plate, but reported ranges are 25mm
(2) .Another global measure of spine alignment is the spino-sacral angle (SSA). The SSA, as
Pelvic Morphology: Its Role in the Differential Causes of Pelvic Pain 201
described by Roussouly (11) is subtended by a line dropped from the C7 vertebral body and
the plane of the sacral end plate.
There are three main measurements that are described with regards to the spino-pelvic
relationship: pelvic incidence is a measure of sacro-pelvic morphology and the pelvic tilt and
sacral slope are measures of sacro-pelvic balance (7, 8). Again, Kuntzs (7) values are cited:
Figure 1. The bony anatomy of the pelvis.
Pelvic incidence (PI) is defined as the angle subtended by a line between the centre of the
femoral head and the centre of the sacral end plate, and a line perpendicular to the sacral end
plate (+54 20).
Pelvic tilt (PT) is the angle subtended by a vertical line draw up from the centre of the
femoral head, and a line between the femoral head and the midpoint of the sacral end plate
(+13 12).
Sacral slope (SS) is the angle between the sacral end plate and a horizontal line (+41
16) Figure 2 demonstrates PI, PT and SS, and, as shown in this figure, they share a
geometric relationship where PI=PT+SS (12).
Despite studies investigating cohorts of patients, both symptomatic, and asymptomatic,
the relationship between these parameters, and how they vary with changing balance is not
entirely understood (7, 12-15). The complexity arises partly because of an individuals
variation, but also because of compensatory mechanism distal to the pelvis, in hips, knees and
ankles, which are difficult to analyse synchronously using radiographs.
The typical history, investigation and treatment of a patient with SPD is demonstrated by
the case below
Figure 2. Pelvic Tilt (PT) is the angle between a vertical line from the femoral head, and a line joining
the femoral head to the middle of the sacral end plate. Pelvic Incidence (PI) is the angle between a line
from the femoral head to the middle of the sacral end plate and a perpendicular line down from the
centre of the sacral end plate. Sacral slope (SS) is the angle between a line parallel to the sacral end
plate and the horizontal. There is a mathematical relationship between these parameters: PI=PT+SS.
Case
History
Mrs X is an 65 year old lady who presented to an outpatient clinic having visited her GP
numerous times with back pain. She had noticed over the past 5 years, increasing back pain,
in particular of her lower back, and inability to stand straight and make eye contact with
friends when conversing. Her walking had deteriorated and she was now requiring the use of
a stick. The main factor restricting her mobility was diffuse pain in her back but more so in
the lower back. She had previously been treated for a lymphoma involving the L1 vertebra
many years earlier but was otherwise fit and well. She reported no abnormal neurology.
Examination
On examination, she stood with good alignment in the coronal plane. She had an obvious
stoop and her head was clearly anterior to her pelvis. Her hips were extended, and on
attempting to assume an upright stance, her posture deteriorated further. Her spine was
extremely stiff and movement restricted in all planes. Her neurology was normal throughout.
Investigation
Full length AP and lateral plain radiographs were obtained (Figure 2). These demonstrate
a plumb line that is 16cm anterior to her sacrum. Her hips are held in extension with an
increase in pelvic incidence, tilt and sacral slope. The normal thoracic kyphosis is flattened.
Treatment
Mrs X had already undertaken a course of physiotherapy organized by her family

physician. She undertook a six month period of focused physiotherapy under the care of a
specialist spinal physiotherapist. It improved her pain slightly, but her ongoing disability
meant that she wanted consideration for surgical intervention. Ultimately she underwent a
corrective osteotomy and posterior instrumented fusion. Post operative radiographs are shown
in Figure 3, together with the respective angles measured on the pre operative radiographs.
Outcome
Following her major spinal surgery, Mrs X had an intensive period of rehabilitation. Six
months postoperatively, she was understandably stiff, but the pain was much improved as was
her overall balance. Walking was enhanced and she was extremely pleased that her posture
had been corrected.
Pathogenesis and Presentation of Sagittal

Plane Deformity
There are a number of conditions that result in SPD. These include Scheuermanns
disease, inflammatory disorders, such as ankylosing spondylitis, tumour, trauma and
degenerative disease.
Scheuermanns disease was described in 1921 (reprint(16)). It is a disease of unknown

aetiology, predominantly affecting adolescents. There is excessive anterior wedging of the
thoracic vertebrae, often resulting in compensatory increased lordosis of the lumbar spine.
Patients may present in adolescence with deformity and pain, but on occasion, it can be
undiagnosed and patients may not present until later in adulthood, with a deformity that has
progressed.
Figure 3. Pre operative lateral radiograph of Mrs X. The plumb line is 16 cm anterior to the sacrum The
pelvic incidence is approximately 80.
Figure 4. Post operative lateral radiograph of Mrs X. The plumb line has been restored to within normal
limits and the pelvic incidence is approximately 50.
Ankylosing spondylitis is a chronic inflammatory arthropathy that typically affects young

men in their twenties and thirties (17, 18). It predominantly affects the spine and the SI joints,
and as the spine becomes more immobile, a fixed kyphosis may occur (19).
Trauma and tumours can also result in vertebral collapse that leads to SPD. However, the
most common group of patients presenting with SPD are the over 60s who develop deformity
secondary to degenerative arthritis. Radiological studies have shown that even in patients
without any pre-existing condition, that age related degeneration can account for as high as 1
progression of kyphosis per year. The plumb line has also been shown to shift forwards with
ageing (20) and there is some evidence (7, 21, 22) to suggest that this is related to symptoms.
Patients present with symptoms of pain and deformity. Their resulting disability can be
great and social interaction, which relies on a forwards gaze, can become deficient. The
symptoms are due to firstly the primary pathology, but also due to the secondary
compensatory mechanisms. Efficient stance and gait rely on maintenance of normal spinal
curves, and deformity can be compensated for to some degree. Much of the compensatory
mechanisms are attributed to changes in spino-pelvic morphology. The intervertebral discs
play a role in maintenance of spinal alignment, but this is easily overcome with progressive
deformity combined with the change in composition of disc with age (23). As a patient begins
to stoop this places excessive strain on the lumbar musculature as they attempt to pull the
spine upright and can lead to aching pains and fatigue. There are limited compensatory
mechanisms in the lumbar spine, and, in an attempt to help maintain an upright posture, other
attributes distal to the lumbar spine are brought into play.
The pelvis and limbs attempt to balance the deformity. The pelvis tilts backwards, thus
extending the hips. In a normal standing posture, the hip hangs in a neutral position. Hip
extension is usually no more than 15 and the pelvic tilt maximizes this. There is further
compensation at the knees, which flex, and the ankles, as they dorsiflex. The combination of
these changes is to attempt to move the position of the spine backwards, so as to allow the
spine to return to a more upright position. These compensatory changes make standing and
gait much less efficient, and one can appreciate how the culmination of these changes can
lead to pelvis, back, and limb pain.
Investigation
Plain radiographs are the main modality for investigating spinal deformity. In the event
that a patient has a congenital cause for the abnormality or presents with symptoms consistent
with neural compression, an MRI scan is a useful adjunct. The radiographs required are full
length films AP and lateral using 36mm cassettes, with the most cranial and caudal landmarks
being C0 and the femoral head respectively. Ideally the patient should have their hips and
knees in a neutral position. This may be limited by stiffness, but the theory is to eliminate the
compensation that is occurring distal to the bottom of the radiograph.
Treatment Options
By the time a patient has been referred to a specialist, they will often have undertaken a
course of physiotherapy organised by a family physician. Often, such physiotherapy is
general, and a further course of therapy may be indicated under the care of a specialist
physiotherapist which in some instances is successful. Treatment is then based on taking into
account a combination of failed conservative measures, patient choice, and the surgeons
input. Ultimately if pain and deformity are significant, then a patient may be offered surgery.
In the older age group there may be significant co-morbidity such as ischaemic heart disease
or respiratory problems that preclude surgical intervention.
Many surgical techniques have been described for addressing SPD. These usually involve
corrective osteotomies where wedges of bone are removed from the spinal column in order to
achieve re-alignment. This is then stabilized with implants. These techniques are well
described in the literature (24-26).
The aim is to restore a patients posture to an upright one, and restore horizontal gaze.
Surgery has potentially significant complications and in some series mortality rates of up to
5.8% have been reported (27).
There is lack of compelling evidence for choice of treatment in SPD and limited long
term functional outcome data. In small cohorts surgical treatments have shown significant
improvements of overall pain and function (25, 28) and high percentages of patient
satisfaction (27, 29). These have been linked to radiological factors including plumb line
correction (30) and improved pelvic tilt (31).
Conclusion
Sagittal plane deformity can manifest in a number of ways, ranging from pain to a
disabling loss of function. There are a wide range of values of the segmental anatomy of the
spine, and as our understanding evolves, more research is being undertaken to better
understand overall spinal alignment and its relationship to the pelvis. The factors that in
recent years have come to light as being a key part of SPD are the changes in the pelvis and
lower limbs. In particular, the parameters of pelvic incidence, pelvic tilt and sacral slope are
being recognized as changing morphological features secondary to other spinal deformity. It
is therefore easy to understand that such global changes can manifest as both back and pelvic
pain. Research has shown that a combination of measurement is required to guide surgical
procedures, and, similarly, that there are a number of radiological factors that appear to be
related to outcome. Ultimately the aim of treatment is to restore alignment and force
distribution through the vertebral column, pelvis and lower limb joints.
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pelvic parameter for three-dimensional regulation of spinal sagittal curves. Eur Spine J.
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Spine (Phila Pa 1976). 2002 Dec 1;27(23):2631-44.
[24] Bridwell KH, Lenke LG, Lewis SJ. Treatment of spinal stenosis and fixed sagittal
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[25] Bridwell KH, Lewis SJ, Lenke LG, Baldus C, Blanke K. Pedicle subtraction osteotomy
for the treatment of fixed sagittal imbalance. J Bone Joint Surg Am. 2003 Mar;85-
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[27] Yang BP, Ondra SL, Chen LA, Jung HS, Koski TR, Salehi SA. Clinical and
radiographic outcomes of thoracic and lumbar pedicle subtraction osteotomy for fixed
sagittal imbalance. J Neurosurg Spine. 2006 Jul;5(1):9-17.
[28] Bridwell KH, Lewis SJ, Edwards C, Lenke LG, Iffrig TM, Berra A, et al.
Complications and outcomes of pedicle subtraction osteotomies for fixed sagittal
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[29] Berven SH, Deviren V, Smith JA, Emami A, Hu SS, Bradford DS. Management of
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Chapter X
Skin Surface Electromyography in

Chronic Prostatitis Type III/
Chronic Pelvic Pain Syndrome:
A Fast and Reliable Way for Diagnosis
Carlos Perez-Martinez*1 and Beatriz Vargas-Diaz Irma2

1
Centro de Urologa Avanzada C.Ur.A, Agricultura Pte, Chih, Mxico
2
Uroneurology and Urodynamics Department,
Centro de Urologa Avanzada C.Ur.A, Chih. Mxico
Abstract
Background and Objective: Pelvic floor muscles (PFM) are hypertonic and unstable
in men suffering Chronic Prostatitis type III/ Chronic Pelvic Pain Syndrome (CP/CPPS).
Our objective is to compare the skin surface electromyography (SSEMG) in patients with
CP/CPPS versus healthy volunteers. Methods: SSEMG were performed with skin surface
electrodes (3M pediatric skin gel patch) 3 cm from anal sphincter in 14 healthy
volunteers as Control Group (CG) and 28 men suffering CP/CPPS as Problem Group
(PG). For SSEMG we used the Verymed Myoexerciser device. Tests were performed
by the same nurse. PG inclusion criteria were CP/CPPS with minimum 6 months with not
pathological origin to explain pain.
All participants signed an informed consent; the study was approved by the ethics
committee. Results: The mean age was 46.36yrs in CG and 44.04yrs in PG(p=0.768).
Logistic regression results as most important variable the Average of resting SSEMG
(PAVRG) (p=0.000). Mean PAVRG was 0.0785 microV SD+/-0.0763 in CG and 0.4243
*
General Director, Centro de Urologa Avanzada C.Ur.A. , Post Address: Av. Agricultura Pte. 514, Cd. Delicias,
Chih. Mxico. 33000. Phonel/Fax. +52639 4725206 and +52639 4743676. E-mail:
carlosperezm@prodigy.net.mx
General Director, Centro de Urologa Avanzada C.Ur.A. , Post Address: Av. Agricultura Pte. 514, Cd. Delicias,
Chih. Mxico. 33000. Phonel/Fax. +52639 4725206 and +52639 4743676. E-mail:
carlosperezm@prodigy.net.mx
212 Carlos Perez-Martinez and Beatriz Vargas-Diaz Irma
microV SD+/-0.2387 in PG. The mean amplitude was 0.0714 microV SD+/- 0.0588 in
CG and 0.4375 microV SD+/-0.5496 in PG(p=0.018). Conclusions: No statistically
significant difference was found in the age between both groups. The most important
variable from the resting SSEMG is PAVRG. The statistically significant difference of
PAVRG shows increased tonus of PFM in men with CP/CPPS, also they have unstable
PFM as shows the higher amplitude of SSEMG (p=0.018). SSEMG in our series has 88%
of sensibility and 65% of specificity. This data suggests some value of resting SSEMG in
diagnosis for CP/CPPS.
Keywords: Chronic Pelvic Pain Syndrome; Pelvic Floor Muscle; Neurophysiologic testing;
Skin Surface EMG; Chronic Prostatitis.
Introduction
The Pelvic Pain Syndrome has been defined by the International Continence Society
(ICS) as the occurrence of persistent or recurrent episodic pelvic pain associated with
symptoms suggestive of lower urinary tract, sexual, bowel or gynecological dysfunction.
There is no proven infection or other obvious pathology (1). The USA NIH consensus
classifies prostatitis as 4 categories (2):
Category I.- Acute bacterial prostatitis

Category II.- Chronic bacterial prostatitis
Category III (2).- Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS),
including 2 subgroups:
Category IIIA.- Patients with objective evidence of inflammation in prostatic
secretions, post-prostate massage urine or semen.
Category IIIB.- Patients with symptoms but no evidence of inflammation in prostatic
secretions, post-prostate massage urine or semen.
Category IV.- Asymptomatic inflammatory prostatitis.
The worldwide prevalence for chronic prostatitis appears to be from 2% to 10%, it

represents a public health problem (2). Chronic abacterial prostatitis is a syndrome
characterized by pelvic pain and voiding symptoms and is poorly defined and understood.
This frustrating disease is more prevalent in ages between 36 to 50 years with no racial
predisposition. Despite the absence of evidence of infection this syndrome is almost always
treated with antimicrobials with poor results (3). The EUA Guidelines describes that this
syndrome must be continuous or recurrent for at least 6 months or regardless the time when is
non-acute or the central sensitization pain mechanisms are well documented (4).
In the last decade, some efforts to discover the etiology of CP/CPPS were done by groups
of researchers: The perineum sensitization (4,5) and musculoskeletal alterations in men with
chronic prostatitis type III/ chronic pelvic pain syndrome (CP/CPPS) have been reported (6).
A previous paper (7) published their results using intra-anal surface electromyography (EMG)
to evaluate the pelvic floor muscles (PFM) in men suffering CP/CPPS, and showed the
resting pelvic floor instability and hyper-tonicity in these patients. Autonomic nerve system
changes had been reported too in these men (8). These four important papers, reading
Skin Surface Electromyography in Chronic Prostatitis Type III 213
together, are very suggestive of the hypothesis of a neurologic component for the origin of
this syndrome.
To date this topic is increasing in popularity, because the diagnostic and prognostic value
for EMG in men with this incapacitating disease. Hetrick et.al. found as the best
measurements, to asses the resting (pre-baseline) PFM EMG, the amplitude and stability (7).
As fast test fashion for EMG office evaluation, we used perineum skin surface
electromyography (SSEMG) in patients with CP/CPPS and compared with healthy
volunteers, in resting position to determine PFM electromyography characteristics in both
groups.
Methods and Participants

Participants: PFM evaluation using SSEMG were performed in 14 healthy volunteers as
Control Group (CG) and 28 men suffering CP/CPPS as the Problem Group (PG). The
participants signed informed consent (9), also the study was approved by the ethics
committee.
The inclusion criteria for PG were CP/CPPS with a minimum of 6 months with not
pathological origin to explain the pain or regardless the time if the syndrome was non-acute
or the central sensitization pain mechanisms were well documented (4). The exclusion criteria
were urine or semen positive cultures, urinary calculi, genitourinary tuberculosis,
genitourinary malignancy, history of pelvic radiation or surgery and congenital genitourinary
diseases. Also participants suffering mental or psychological disorders were excluded.
Healthy volunteers were accompanying persons or healthy men consulting for check up; they
were evaluated free of charge, we explained them the results of this study, if requested.
A Spanish validated version (10) of the National Institutes of Health Chronic Prostatitis
Symptom Index (NIH-CPSI) was completed by all participants. Sub domains of Pain, Urinary
Symptoms and QoL Impact were recorded (3). Also urine and semen cultures, PSA,
abdominal sonogram of the prostate, uroflowmetry and residual post void volume were
assessed.
Procedure for EMG: For resting SSEMG we used the Verymed Myoexerciser device,
originally designed for biofeedback, with skin surface electrodes (3M pediatric skin gel
patch) placed 3 cm from anal sphincter. The skin was prepared as follow: After shaving the
hair using a disposable razor, the nurse washed the skin with surgical soap and sterile water,
and then dried scrupulously the perineum with a disposable towel. Before putting the patch on
the skin the nurse added 0.5 cubic centimeter of highly conductive electrolyte saline base gel
at the center of the patch.
All participants emptied their bladder before the test and relaxed by 15 minutes, while
they get, from the nurse, an explanation about the procedure for EMG. With patient/volunteer
resting in sit position, semi-reclined, with a pillow flexing knees and thighs resting free
laterally. All tests were performed by the same nurse specially trained in EMG and
biofeedback, in a special laboratory inside of our medical center. The nurse was blinded to the
subject health status. Participants were never able to see the EMG screen display. Records
were collected using a Data Base Excel and analyzed by SPSS10.0 software.
Measures: For measurement of the pelvic floor muscles, SSEMG was recorded by 60
seconds in rest position. The assessment of myoelectric characteristics integrated in SSEMG
were: a) mVMAX, maximum micro-voltage in rest; b) PAVRG, average micro-voltage in
rest; c) MIN, minimum micro-voltage in rest and; d) AMPLITUDE.
Statistical Analysis: As shows Table 1, statistical analyses of pelvic floor muscle resting
EMG between two groups included independent sample mean differences t-tests. To
determine the reliability of measurements from SSEMG to predict group membership of each
individual subject in the study, PG vs CG, we conducted a logistic regression (see Table 2).
Table 1. Mean resting SSEMG readings by group
Variable Problem G Control G t-test sig. Logistic

Mean Mean regression sig.
mVMAX 0.8846 0.1343 0.006 0.265
pAVRG 0.4243 0.0785 0.000 0.010
MIN 0.3171 0.0657 0.001 0.028
AMPLITUDE 0.4375 0.0714 0.016 0.018
Problem G, men with CPPS: Control G, healthy volunteers; mVMAX, maximum micro-voltage in rest;
PAVRG, average micro-voltage in rest (resting muscular tonus); MIN, minimum microvoltage in
rest; AMPLITUDE, muscular stability.
Table 2. Classification of Participants by SSEMG Characteristics in Logistic Regression

Equation
Observed Status Predicted Status

Case Percentage Correct
CG PG
CG 11 3 78.6
PG 1 27 96.4
Overall Percentage 90.5
a The Cut value is .600
Results
The mean age was 46.36 yrs SD+/-10.46 in CG and 44.04 yrs SD+/-15.39 in PG
(p=0.768). Based on the EMG curves, in the Control Group 3/14 (21.4%) SSEMG records
were abnormal compared with the Problem Group where 22/28 (78.6%) SSEMG records
were abnormal.
The logistic regression results as stronger variable the PAVRG (p=0.000)(see Table 1).
The mean PAVRG was 0.0785 microV SD+/-0.0763 in CG and 0.4243 microV SD+/- 0.2387
in PG. The mean PAVRG results 0.3458 microV higher in PG (p=0.000). This measurement
represents the resting tonus of PFM. The amplitude of SSEMG was 0.0714 microV SD+/-
0.0588 in CG and 0.4375 microV SD+/-0.5496 in PG. Amplitude results 0.3661 microV
higher in PG (p=0.018), it represents the resting myo-electric activity of PFM (muscular
stability).
Table 3 shows differences between both groups in NIH-CPSI sub-scores that results with
statistically significant differences for the Total NIH-CPSI score (p=0.000) and Pain
(p=0.000), but not statistically significant differences for Urinary Symptoms (p=0.997) and
Impact on Quality of Life (p=0.500).
Table 3. Group Statistics for NIH-CPSI and sub domains
Case N Mean Std. Deviation Std error Mean

NIH Score CG 14 7.64 3.93 1.05
PG 28 24.96 5.05 .95
Pain CG 14 1.71 1.59 .42
PG 28 14.89 2.11 .40
Sympton CG 14 3.36 3.23 .86
PG 28 4.07 2.75 .52
Qol CG 14 2.57 1.87 .50
PG 28 6.07 2.89 .55
Table 4 shows a comparison of severity of CP/CPPS and EMG results based on

percentiles of the duration, is easy to see different scores of NIH-CPSI between the 50th
percentile and 75th percentile of this cohort, corresponding to 6 months and 27 months of
duration respectively. Just mayor changes were found in PAVRG (PFM resting tonus) 0.27
microV and 0.45 microV respectively, and Amplitude (PFM instability) 0.20 microV and
0.32 microV respectively. Also NIH-CPSI total increases from 22 points to 26.5 points from
50th to 75th percentiles, as well as pain increases from 13 points to 16 points.
Table 4. Descriptive Statistics by Percentiles of Duration months). 25th percentile (0

Mo) includes the Control Group
N Percentiles
25th 50th Median 75th
MONTHS 42 .00 6.00 27.00
NIHSCORE 42 8.75 22.00 26.50
PAIN 42 3.00 13.00 16.00
SYMPTOM 42 1.00 3.00 6.25
QoL 42 2.00 4.50 8.00
PAVRG 42 0.09 .2700 .4500
Amplitude 42 0.08 .2000 .3200
Urinary Symptoms and the Impact on Quality of Life were the higher changes regarding
duration of this syndrome; these changes were from 3 points to 6.25 points for Urinary
Symptoms and from 4.5 points to 8 points for Quality of Life, from 6 months to 27 months,
respectively.
The PFM anatomy has been widely described (11), but its functioning and interrelations
with another organs and systems are partially defined (12,13). Morphological researches
showed PFM innervations recently discovered (14) with pathological implications, not yet
clarified. In the last decade, because of the use of neurophysiologic tests (15), knowledge of
CP/CPPS physiopathology (16) increased enormously, including the perineum
hypersensitization in this group of patients (5), the musculoskeletal alterations (6,7) and the
autonomic nerve system changes (8). This new approach of CP/CPPS patients opens the
hypothesis of a neurologic origin of this syndrome, and gives fresh clues for diagnosis and
new treatment alternatives.
Surface EMG is not usually used in CP/CPPS patients. However, Hetrick et. al. showed
the advantage of surface EMG as useful tool in diagnosis of CP/CPPS patients. This group
reported the resting pelvic floor instability and hyper-tonicity as a reliable surface EMG
measurement for pelvic floor muscle dysfunction in men suffering CP/CPPS (7). In this
paper, researchers used intra-anal surface sensor. Because of the discomfort caused by intra-
anal device in some men, we try to assess the reliability of EMG using skin surface
electrodes. In the same paper researchers concluded that the best measurement is
prebaseline rest EMG, because of this; we designed a fast fashion EMG test in rest, no using
the full Glazer protocol. Since surface skin patches for EMG are less "electric sensitive"(17)
than intra anal electrodes, we used a "meticulous" technique to prepare the skin as well to fix
the skin patches, using the "ten years experience" that our nurse-technician has, hoping in this
way, to avoid interference and get good quality EMG registry.
Figure 1. TOP. Resting skin surface electromyography (SSEMG) in healthy volunteer. BOTTOM. The
resting SSEMG in CPPS man, the amplitude and average are higher than the data recorded in healthy
men.
Is well known, that the intra-anal EMG records are easier recorded and reproducible, but
is more comfortable for male patients the use of skin surface EMG (17). Despite the
simplicity of the device used for SSEMG in our paper, originally designed for biofeedback,
and only resting electromyography assessment, our results are similar to previously reported,
in spite of the use of skin surface electrodes. In her paper, Heraceck et. al. showed that the
prebaseline mean 60 sec rest amplitude (PREBLM) was 6.471 in Control Group and 10.429
in CP/CPPS group (p=0.016) compared with our results of mean AMPLITUD was 0.0714 in
Control Group and 0.4375 in CP/CPPS Group (p=0.018). Thus, both papers show that men
suffering CP/CPPS have PFM instability (see Fig. 1). Also men with CP/CPPS have
increased tonus of PFM (statistically significant difference of PAVRG p=0.000). As Table 4
shows, the Urinary Symptoms were the higher changes regarding duration of this syndrome
increasing from 3 points to 6.25 points from 50th to 75th percentiles, as well as Quality of Life
Impact increases from 4.5 points to 8 points, respectively. It is interesting to observe in this
cohort, corresponding to 6 months (50th percentile) and 27 months (75th percentile) of
duration, the changes in PAVRG (PFM resting tonus) from 0.27 microV to 0.45 microV
respectively, and the Amplitude (PFM instability) changes from 0.20 microV to 0.32 microV
respectively. Then, the duration of CP/CPPS increase the impact on the quality of life because
the raise of urinary symptoms and the instability and tonus of the PFM.
Technical difficulties for skin surface electrodes. Regarding the EMG using intra-anal
probe (9,10), Mesin & Gervasio wrote that detection volume of EMG recording systems from
sphincter muscles extends more in the axial than in the depth direction and is affected by
many parameters (18).
In the past the assessment of the myo-electric activity of the external anal sphincter has
long been restricted to investigating patients by invasive tools such as needle EMG, while less
invasive techniques have been regarded as non-suitable for diagnostic purposes (19). The anal
probe for EMG is today more popular, because of its simplicity it remains as the preferred
invasive procedure (20), including diagnostic procedures. Also because better results may be
obtained when the therapist is well trained and experienced (21). Our opinion is that the same
situation is happening with the SSEMG. Skin surface electrodes in perineum are difficult to
use for EMG. Having performed surface EMG for urodynamics as well as EMG biofeedback
in many patients we experience technical difficulties before and got experience and increase
our skills. We placed the pediatric EMG electrodes 3 cm from the anal sphincter. Most
patients sit on an area with a thick fat layer, which could hamper the EMG signaling. This is
worse in patients anxious and nervous; when they move their bodies, the electrodes lose
contact with the skin. To avoid this, we designed a special technique wrote before, to get
enough quantity of signals from the myoelectric activity. The experience, increase of skills,
training of the technicians and doctors, in addition to the knowledge of the behavior, concerns
and idiosyncrasy of our male patients, have been very useful for design a special technique
and a good pretest explanation as a motivational session, brief but comprehensive. In this way
the participation of male patients in a fast non invasive procedure, is superb. These facts make
easy the test increasing the accuracy of SSEMG. Larger studies should be conducted to
compare the accuracy of needle EMG versus intra-anal probe versus SSEMG. Only in this
way is possible to know truly the accuracy of each fashion of PFM EMG. From the Control
Group 3/14 (21.4%) EMG records were abnormal compared with the Problem Group where
22/28 (78.6%) EMG records were abnormal. The SSEMG in our series has 88% sensibility
and 65% of specificity to diagnose CP/CPPS. Despite low signal and low intensity, SSEMG
is enough to find differences between normal and abnormal myo-electric activity of

PFM, with a predictive value of 79%.
Conclusion
In our series the most important variable from the SSEMG is PAVRG regardless of the
mean age of both groups (p=0.768). Men suffering CP/CPPS have an increased tonus of
PFM, also it is unstable in resting position. These data suggest that resting SSEMG would
have some value in the diagnosis of CP/CPPS. The SSEMG in our series has 88% of
sensibility and 65% of specificity to diagnose CP/CPPS, with a predictive value of 79%.
Should our results be confirmed by larger studies using resting SSEMG, this would open the
possibility for the use of a "non invasive" alternative technique for EMG in CP/CPPS
patients.
References
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Index
amino, 88
A amplitude, 53, 83, 91, 92, 188, 210, 211, 212, 214,
215
abuse, 104
amputation, 100
access, 11, 36, 37, 186
anaerobic bacteria, 22
acetabulum, 198
anal fissures, 84, 90, 94
acetylcholine, 94, 95, 188, 192
analgesic, 27, 43, 64, 67, 142
achilles tendon, 50
anatomic site, 149
acid, 30, 89, 103, 116
anatomy, 25, 141, 147, 164, 169, 178, 198, 199, 205,
action potential, 85, 116
213
acupuncture, 95, 97, 101, 104, 163, 190
androgen, 154, 162
acute infection, 152, 159
anesthetics, 28, 35, 94, 190
adaptation, 47, 72, 165
angiogenesis, 121
adduction, 8, 18
ankles, 50, 200, 204
adductor, 8, 191
ankylosing spondylitis, 193, 201, 206
adenomyosis, 131, 133, 134, 135, 140, 143, 144,
ANS, 16, 18
145, 146, 172, 175
anterior cingulate cortex, 153
adhesion, 19, 23, 24, 25, 88, 107, 130, 132, 140, 141,
antibiotic, 23, 151, 160, 169
147, 148, 172, 173, 175, 178, 183, 185, 186
antibody, 55
adipose, 189
anticoagulation, 26, 190
adjustment, 30, 88, 168
anticonvulsant, 30, 162
adolescents, 70, 143, 202, 206
antidepressant, 162, 176
adulthood, 202
antidepressants, 27, 29, 30, 32, 34, 176, 182
adults, 206
antiepileptic drugs, 27
advancement, 34
antigen, 45, 158, 167
adverse effects, 24, 25, 30, 31, 32, 33
anti-inflammatory drugs, 1, 27, 45, 69, 176
adverse event, 31
antimicrobial therapy, 159
aerobic exercise, 93
anus, 10, 12, 78, 79, 81, 115
aetiology, 183, 193, 202
anxiety, 90, 99, 116, 143, 176, 188, 189, 191
afferent nerve, 85, 86, 133
aorta, 3
afferent nerve fiber, 133
aplasia, 20
age, 23, 24, 43, 49, 71, 73, 84, 130, 151, 152, 172,
apoptosis, 161, 165
177, 197, 203, 204, 205, 206, 207, 209, 212, 216
appendectomy, 3, 4, 5
agonist, 83, 144, 177
appendicitis, 26, 135
alcohol abuse, 186
aromatic compounds, 47
algorithm, 41
arteries, 133
allergy, 190
artery, 38
alpha blocker, 161
Asia, 84, 104
alpha interferon, 40
assessment, 37, 71, 72, 95, 122, 163, 175, 189, 193,
alters, 44
198, 206, 212, 215
amenorrhea, 20
222 Index
asthma, 108, 171

asymmetry, 12, 43, 44, 48, 49, 50, 52, 54, 55, 58, 59, C
62, 63, 70
calcification, 66, 69, 159
asymptomatic, 19, 20, 21, 22, 23, 37, 110, 135, 142,
calcitonin, 117, 121, 122, 139
152, 158, 167, 198, 199, 205, 206
calcium, 28, 70, 88, 188
ataxia, 30
canals, 46, 47, 110
atrophic vaginitis, 10
cancer, 19, 22, 49, 154, 162
atrophy, 9, 25, 77, 83, 118
cancer cells, 154
autonomic activity, 173
candidates, 174
autonomic nervous system, 18, 108, 115, 121, 122,
candidiasis, 9
153, 163
capsule, 18
awareness, 160, 193
carcinoma, 132
axial skeleton, 198
cardiovascular system, 118
axonal degeneration, 192
cartilage, 45, 63, 64, 70, 198
axons, 29, 116
cartilaginous, 198
case study, 163
B catalysis, 47
causal relationship, 154
back pain, 43, 46, 47, 49, 54, 58, 60, 68, 69, 70, 71, causalgia, 99
72, 73, 82, 87, 101, 103, 151, 172, 193, 200, 205 cecum, 110
bacteria, 13, 150, 152, 167 cell body, 116
basal forebrain, 117 cell line, 117, 123
basal layer, 134 central nervous system, 1, 31, 95, 113, 125, 136,
base, 81, 87, 191, 211 164, 173
baths, 28 centralisation, 46, 65
beams, 46 cerebral cortex, 86
behaviors, 28 cerebrospinal fluid, 33
beneficial effect, 160, 162 cervical radiculopathy, 103
benefits, 142, 160 cervix, 15, 16, 19, 20, 22, 110, 122
benign, 22, 129, 130, 154, 161, 165, 168, 169 chemical, 19, 23, 46, 51, 65, 66, 86, 94, 115, 119,
bias, 169 122, 126, 154, 192
biochemistry, 103 chemical properties, 66
biofeedback, 28, 40, 177, 211, 215 chemical reactions, 46
biological activity, 23, 46, 47 chemicals, 177
biomarkers, 119, 122 chemokines, 168
biomechanics, 44 chemotaxis, 65
biopsy, 13, 22, 24, 169, 175 Chicago, 168
bladder cancer, 123 chicken, 138
bleeding, 19, 20, 22, 26, 132, 174, 177, 190 childhood, 45, 84
blood, 3, 18, 19, 20, 23, 26, 30, 44, 45, 65, 67, 103, children, 70
124, 133, 143 China, 155
bone, 25, 49, 64, 68, 79, 83, 89, 91, 132, 204 Chlamydia trachomatis, 22, 39
bowel, 25, 81, 104, 109, 110, 111, 114, 131, 135, chronic lymphocytic leukemia, 71
141, 159, 172, 173, 174, 180, 210 circulation, 60
bradykinin, 139 clarity, 194
brain, 23, 32, 33, 34, 116, 117, 132, 164, 173 classification, 23, 27, 37, 39, 84, 100, 131, 143, 149,
brainstem, 86, 111 150, 157, 160, 166
branching, 116 clothing, 28
Brazil, vii, 185 clusters, 45, 64, 65
breakdown, 65 coccydynia, 77
breathing, 91, 189 coccyx, 3, 11, 80, 198
bursitis, 4 coding, 122
cognition, 142
Index 223
colic, 86 cross-sectional study, 104, 166, 167

colitis, 116, 120 culture, 28, 68, 71, 150, 151, 152, 155, 157, 160
collagen, 45, 66, 71, 73, 88 cure, 108, 161
colon, 16, 118, 123, 124, 125 cycles, 20, 23, 56
communication, 9, 33, 86 cycling, 117
community, 127, 180 cyclooxygenase, 146, 161
comorbidity, 172 cyclophosphamide, 126
comparative analysis, 52 cyst, 19, 22, 25, 26, 35, 44, 45, 47, 48, 63, 64, 65, 66,
compensation, 204 67, 68, 70, 71
complexity, 199 cystoscopy, 112
compliance, 177 cytokines, 111, 121, 138, 140, 152, 153, 166, 168
complications, 23, 25, 26, 35, 36, 66, 93, 132, 190,
205
composition, 64, 204 D
compounds, 46, 47, 162
compression, 3, 4, 6, 10, 11, 15, 19, 20, 24, 37, 44, daily living, 174
68, 71, 83, 88, 163, 187, 188, 189, 190, 194, 204 dance, 84
computer, 53, 54, 55 database, 127, 179
conceptual model, 127 defecation, 12, 17, 81, 173, 174
conditioning, 136 defects, 64, 66, 141
conflict, 43, 45, 46, 49, 52, 53, 56, 57, 58, 62, 63, 64, deficiencies, 153
66, 69 deficiency, 9, 29, 40, 88, 89, 117, 155, 162
congenital malformations, 20 deficit, 5, 32, 88
conjunctiva, 132 degenerative arthritis, 203
connective tissue, 21, 85, 91, 96, 114 degradation, 26, 46, 62, 64, 88, 188
conscious perception, 115 depolarization, 188
consciousness, 176 deposition, 70
consensus, 163, 166, 178, 193, 210 deposits, 64
constipation, 32, 84, 109 depression, 86, 89, 90, 99, 132, 133, 154, 159, 176,
construction, 46, 66 186
consulting, 127, 211 depressive symptoms, 155
contact dermatitis, 29, 39 depth, 51, 99, 111, 121, 134, 135, 176, 215
contraceptives, 133, 136, 138, 147, 177 derivatives, 33, 46, 47
contracture, 91, 152 dermatitis, 9
control group, 44, 48, 49, 55, 58, 59, 60, 61, 63, 163, dermatologist, 39
174, 178 dermatoses, 9
controlled trials, 160, 162 descending colon, 16
controversial, 155, 173 desensitization, 29
convergence, 15, 115 destruction, 22, 34, 63, 64, 65, 66, 118, 131
cooling, 90, 153, 166 destructive process, 43
coordination, 90 detectable, 139
corpus luteum, 19 detection, 13, 66, 91, 93, 129, 138, 140, 175, 181,
correlation, 56, 58, 62, 66, 70, 71, 73, 90, 114, 123, 187, 188, 191, 215
148, 155, 158, 159, 173, 206 detergents, 28
correlations, 58, 62, 74, 101 diabetes, 6
cortex, 85 diabetic neuropathy, 31, 39
corticosteroid therapy, 161, 168 diabetic patients, 73
corticosteroids, 27, 32, 35 diagnostic criteria, 7, 11, 12, 120
cost, 1, 94, 151, 175, 177 diagnostic markers, 122
cotton, 11, 13, 14, 15, 28, 34 diaphragm, 78, 79, 88, 90, 95, 131, 191
counseling, 35, 177 diet, 13, 28, 84, 86, 178
covering, 187 dietary supplementation, 183
creatinine, 168 differential diagnosis, 5, 23, 188, 189, 194
224 Index
disability, 68, 69, 129, 154, 169, 171, 172, 177, 201, electron, 147
204 electrophoresis, 46
discitis, 73 ELISA, 55
discomfort, 9, 10, 29, 44, 48, 63, 76, 80, 90, 94, 114, elongation, 96
132, 133, 142, 149, 157, 163, 175, 189, 192, 214 e-mail, 43
discrimination, 112, 192 emboli, 21, 38
discs, 68, 69, 71, 204, 207 embolism, 19
diseases, 9, 11, 15, 18, 19, 23, 66, 88, 129, 130, 135, embolization, 21, 38
136, 137, 141, 165, 175, 176, 192, 211 emergency, 1, 26
diskitis, 68 EMG, 85, 92, 93, 103, 210, 211, 212, 213, 214, 215,
dislocation, 44, 47 216
disorder, 8, 9, 10, 44, 77, 100, 108, 109, 111, 114, emotional experience, 1
119, 122, 135, 163, 174 employment, 172
displacement, 4, 15, 63 encouragement, 68
distress, 177 endocarditis, 73
distribution, 5, 62, 115, 116, 125, 174, 176, 205 endocrine, vii, 151, 161, 185, 186, 188
dizziness, 30 endocrine system, vii, 185, 186
doctors, 45, 68, 215 endorphins, 27, 28
doppler, 155 energy, 21, 32, 47, 63, 85, 163, 177, 181
dorsal horn, 86, 99, 116, 119, 136 entrapment, 4, 5, 11, 35, 36, 37, 41, 81, 151
dosage, 30 environment, 14
dosing, 31 enzymatic activity, 65
double-blind trial, 165 enzyme, 64, 66
down-regulation, 136 enzymes, 23, 24, 46, 65
drainage, 23, 25, 26 epidemiology, 84, 104, 142, 143
drawing, 65 epididymis, 157
drug therapy, 105 epilepsy, 30
drugs, 24, 27, 28, 31, 33, 46, 47, 51, 67, 136, 162, episiotomy, 40
190 epithelial cells, 139
drying, 28 epithelium, 34, 110, 124, 154
dura mater, 64 EPS, 150, 152, 157, 158
durability, 44, 64 equilibrium, 96
dyes, 28 equipment, 54, 159
dysmenorrhea, 20, 24, 110, 129, 130, 131, 133, 134, erosion, 13
135, 141, 142, 143, 144, 145, 146, 171, 172, 173 estrogen, 9, 23, 29, 112, 114, 117, 118, 122, 123,
dyspareunia, 20, 23, 24, 29, 107, 110, 129, 130, 133, 124, 125, 126, 127, 129, 133, 138, 139, 140, 188
134, 141, 171, 172, 173, 174, 191, 192 ethanol, 133
dysuria, 129, 130, 131, 132, 141, 174 ethics, 111, 209, 211
etiology, vii, 23, 68, 75, 109, 111, 113, 118, 135,
140, 143, 149, 150, 151, 160, 164, 174, 177, 210,
E 217
Europe, 38, 84, 104
economic problem, 1, 133
evidence, 24, 33, 38, 84, 85, 94, 98, 99, 108, 113,
economic status, 151 114, 118, 119, 121, 126, 127, 138, 140, 143, 150,
ectopic pregnancy, 20 155, 157, 159, 165, 173, 175, 176, 177, 178, 179,
edema, 78, 91
180, 181, 188, 194, 203, 205, 210
editors, 101, 165, 168
evil, 101
education, 28, 93 evolution, 26
ejaculation, 12, 81, 155, 163, 166, 169 examinations, 43, 66, 130, 141
electricity, 49, 53, 54, 58, 60, 61, 62
excision, 34, 71, 140, 141, 146, 147, 148, 177, 180,
electrodes, 53, 54, 209, 211, 214, 215, 217
182, 183
electrolyte, 211 excitability, 116, 127
electromagnetic, 163
excitation, 14
electromyography, 40, 209, 210, 211, 214, 215, 217
Index 225
exclusion, 175, 211 France, 75, 217

exercise, 7, 17, 27, 93 freedom, 31
expertise, 98 friction, 4, 10
exposure, 17, 28, 32, 36, 148, 166 functional changes, 108
external environment, 14 fusion, 71, 201, 207
external oblique, 3, 6
extracellular matrix, 68
extravasation, 116, 118, 119 G
gait, 204
F ganglion, 115, 117, 120, 122, 123, 124, 125
gastrointestinal tract, 172, 175
facial pain, 103, 187 gel, 47, 49, 50, 51, 209, 211
fallopian tubes, 15, 18, 108, 110, 114 generalized anxiety disorder, 30
families, 28 genes, 66, 153, 169
family physician, 201, 204 genitals, 2, 41, 191
family planning, 130, 142 genitourinary tract, 150
fascia, 3, 9, 17, 36, 77, 83, 85, 98, 114, 172, 187 genotype, 153
fat, 78, 215 geometry, 64
fatty acids, 183 Germany, 129
fear, 190 gestation, 26
feelings, 13, 14, 28 gland, 16, 47, 157, 169
female rat, 117, 119, 120, 122, 124 glasses, 157
femur, 8 glutamate, 139
fertility, 38, 141, 144, 150 gluteus maximus, 81
fever, 21, 22, 26 graph, 54
fibroblasts, 45, 64, 121 group membership, 212
fibroids, 20, 21, 24, 26, 38, 129, 135, 137, 179 group therapy, 177
fibromyalgia, 30, 92, 101, 103, 105, 123, 151, 153, growth, 20, 22, 33, 65, 121, 123, 129, 138, 140, 154,
166, 194 173
fibrosis, 69, 72, 77, 83, 152 growth factor, 123, 129, 138, 140
fibrositis, 92, 194 guidance, 33
fibrous cap, 79 guidelines, 160, 174
fibrous tissue, 95 gymnastics, 84
films, 204
fish, 183
fish oil, 183 H
fixation, 11
flatulence, 133 hair, 211
harbors, 152
flex, 54, 204
headache, 29, 89, 133, 174
flexibility, 27, 44, 64, 65
flora, 22, 157 healing, 47
fluctuations, 113, 117, 119, 122, 132, 168 health, 1, 36, 103, 152, 154, 165, 166, 174, 175, 179,
180, 181, 193, 211
fluid, 44, 64, 71, 129, 133, 136, 138, 140, 146, 147,
health care, 1
148, 150, 158, 159, 166
fluoxetine, 39 health status, 211
folic acid, 88, 103 heart rate, 30
height, 54
foramen, 7, 8
helplessness, 154
force, 44, 77, 105, 123, 205
Ford, 102 hematoma, 5, 20, 190
formation, 45, 51, 70, 71, 130, 139, 140, 147, 183, hematomas, 3
hemorrhage, 20, 26
190
formula, 53, 55, 56 hemorrhoids, 17, 84, 94
fragments, 65 hepatitis, 49
226 Index
hernia, 4, 5, 6, 7, 45, 48, 62, 63, 64, 66, 189 image, 52, 66, 198
hernia repair, 4, 5 imagery, 64
herniated, 70, 72, 73 images, 66
herniated nucleus pulposus, 70 imbalances, 17, 161
herniorrhaphy, 3 immigration, 139
herpes, 9 immune response, 67
herpes simplex, 9 immune system, 45, 64, 65
herpetic keratitis, 71 immunoglobulin, 64, 66, 71
heterogeneity, 108, 149 immunohistochemistry, 118, 125
hip abduction, 18 immunomodulatory, 33, 43, 65, 67, 68
hip joint, 53, 54, 55 immunoreactivity, 119, 124
hippocampus, 117 implants, 19, 25, 49, 111, 132, 136, 141, 146, 178,
histamine, 117, 122, 123, 135, 139, 188 181, 205
histogenesis, 71 improvements, 30, 205
histology, 112 impulses, 33, 53, 86, 136
historical data, 180 in vitro, 68, 117, 138
history, 13, 24, 40, 49, 64, 68, 75, 90, 92, 93, 110, in vivo, 68, 71, 73, 117
112, 114, 141, 152, 155, 156, 173, 174, 200, 211 incidence, 22, 39, 84, 104, 110, 125, 127, 137, 172,
hopelessness, 159 178, 179, 197, 199, 201, 202, 203, 205, 206
hormone, 25, 89, 119, 136, 140, 144, 148 individuals, 14, 114, 160, 189, 199
hormones, 108, 113, 114, 116, 118, 121, 122, 123, induction, 95, 111, 126, 139
134, 188 infection, 10, 11, 13, 19, 22, 64, 72, 84, 109, 117,
hub, 190 136, 149, 150, 151, 152, 159, 169, 174, 190, 197,
human, 14, 36, 70, 71, 72, 103, 111, 118, 121, 122, 210
124, 126, 130, 144, 145, 146, 154, 206 infertility, 20, 22, 23, 24, 110, 121, 130, 134, 145,
Hunter, 180 177, 181
hyaline, 21 informed consent, 209, 211
hydrophilicity, 45 ingestion, 190
hygiene, 13, 28 inguinal, 2, 3, 4, 5, 6, 7, 110
hyperactivity, 133 inguinal hernia, 5
hyperesthesia, 6, 7, 8 inhibition, 25, 45, 67, 96, 137
hyperplasia, 145, 152 inhibitor, 71, 146, 148, 161
hypersensitivity, 90, 113, 116, 120, 153 initial state, 95
hyperthermia, 95 initiation, 144
hypertrophy, 123, 152 injections, 37, 64, 73, 76, 94, 100, 102, 163, 190
hypnosis, 163 injure, 188
hypothesis, 66, 85, 99, 102, 138, 211, 214 injuries, 3, 25, 84, 153, 191
hypothyroidism, 103 injury, iv, 1, 4, 17, 33, 49, 63, 70, 75, 84, 112, 113,
hysterectomy, 4, 5, 6, 7, 21, 25, 38, 88, 134, 145, 136, 154
148, 179, 193 insects, 13
insertion, 10, 25, 94, 192
integrity, 11, 14, 113
I intercourse, 10, 29, 133, 173
interdependence, 56
ibuprofen, 142 interference, 30, 46, 214
ice pack, 28
interferon, 29, 33, 40
ice packs, 28
internal oblique, 3, 189
ideal, 177 interneuron, 116
identification, 13, 112, 119 internists, 164
idiopathic, 10, 112, 123
interrelations, 213
IL-8, 158
interstitial cystitis, 9, 77, 97, 100, 101, 104, 107, 120,
ileum, 110 121, 122, 123, 124, 125, 126, 132, 148, 153, 167,
iliac crest, 3, 4
168, 172, 174, 180, 185, 186, 191, 192
ilium, 198
Index 227
intervention, 142, 177 lichen planus, 10

intestine, 16, 132, 137 lifetime, 151
introitus, 10 ligament, 2, 5, 6, 9, 11, 16, 36, 63, 80, 88
involution, 66 ligand, 117
ions, 44, 188 light, 6, 14, 27, 118, 189, 198, 205
ipsilateral, 189 lithotripsy, 99
iron, 88 liver, 31, 46, 47, 51
irradiation, 4, 8 local anesthetic, 7, 47, 94, 190, 194
irritable bowel syndrome, 77, 107, 110, 114, 122, localization, 33, 132, 143, 157
125, 132, 172, 174, 185, 186, 192 longevity, 45, 66
ischaemic heart disease, 204 lordosis, 88, 186, 198, 202
ischemia, 3, 17, 24, 109, 188, 190 lumbar laminectomy, 70
ischium, 79, 198 lumbar spine, 5, 68, 70, 71, 73, 202, 204, 206
isolation, 28, 130 lymphocytes, 45, 64
issues, 155 lymphoma, 201
Italy, 84, 104, 171 lysis, 147, 178, 183
J M
joint pain, 89 macrophages, 23, 45, 64, 129, 136, 138, 139, 146
joints, 15, 17, 45, 49, 54, 132, 188, 189, 198, 203, magnetic field, 46
205 magnetic resonance, 24, 38, 68, 70, 144, 153
magnetic resonance imaging, 24, 38, 68, 70, 144
magnitude, 1
K majority, 10, 51, 112, 115, 150, 154, 190
malignancy, 211
knees, 50, 96, 200, 204, 211 malignant tumors, 26
kyphosis, 198, 201, 203, 206 man, 151, 167, 214
management, 13, 30, 33, 38, 40, 73, 98, 100, 103,
L 111, 119, 121, 143, 146, 160, 163, 164, 167, 168,
169, 179, 180, 181, 182, 183, 185, 187, 193, 194,
laboratory tests, 92 195
laminectomy, 64, 66, 70 manipulation, 36, 194
laparoscopy, 23, 24, 27, 110, 112, 122, 140, 141, marrow, 71
172, 175, 178, 179, 181, 193 mass, 20, 26, 141, 142
laparotomy, 178 mast cells, 112, 113, 117, 121, 123, 138, 139
latency, 115 matrix, 24, 71, 148
lead, 5, 26, 43, 44, 45, 46, 47, 48, 62, 63, 66, 68, 78, matrix metalloproteinase, 24, 71, 148
87, 98, 110, 116, 119, 131, 137, 138, 152, 160, matter, iv, 171, 173
164, 171, 172, 175, 186, 191, 192, 204 measurement, 52, 53, 55, 56, 58, 62, 90, 105, 155,
legs, 8, 87, 133, 188 181, 187, 189, 205, 212, 214
leiomyoma, 144 measurements, 50, 167, 187, 189, 195, 199, 206,
lens, 13 211, 212
lesions, 9, 23, 24, 85, 94, 110, 111, 129, 130, 131, medial epicondyle, 187
132, 135, 137, 138, 139, 140, 143, 146, 147, 152, median, 79, 112
173, 175, 181 mediation, 126
lethargy, 30 medical, 1, 20, 25, 34, 47, 49, 68, 75, 78, 97, 98,
leukocytosis, 22 105, 108, 112, 141, 148, 151, 169, 171, 172, 174,
levator, 9, 17, 38, 77, 78, 79, 80, 87, 88, 94, 95, 97, 182, 187, 211
100, 102, 112, 114, 121, 123, 125, 186, 191 medical care, 171, 187
libido, 25, 97 medical history, 174
lichen, 10 medication, 161
medicine, 43, 63, 64, 65, 67, 68, 69, 98, 103
228 Index
memory, 45, 53 neurons, 29, 86, 87, 115, 117, 118, 120, 122, 123,
menarche, 20, 23 124, 125, 127, 136
meninges, 45 neuropathic pain, 13, 27, 29, 30, 31, 34, 41, 86, 99,
menopause, 21, 89, 112 136, 139, 142, 151, 162, 165, 176
menorrhagia, 111, 134 neuropathy, 11, 40, 88, 99
menstruation, 23, 86, 110, 132, 133, 141, 142, 144 neuropeptides, 29, 86, 117, 126, 138
mesenteric vessels, 138 neurophysiology, 12, 108, 147
mesentery, 111 neurotransmission, 124
messenger ribonucleic acid, 144 neurotransmitter, 30
meta-analysis, 24, 25, 114, 173 neurotransmitters, 116, 139
metabolic changes, 63 neutral, 204
metabolism, 68, 73 nocturia, 11, 112, 117, 159
metabolites, 19, 26 nodules, 141, 146, 173, 180, 192
metabolized, 51 non-steroidal anti-inflammatory drugs, 136
metalloproteinase, 71, 148 norepinephrine, 88, 162
meter, 194 normal children, 206
methodology, 150, 175 nuclei, 117
methylprednisolone, 40 nucleus, 44, 45, 63, 70, 71, 118, 120
mice, 116, 117, 118, 122 nutrition, 66, 191
microorganisms, 22, 151, 152, 160 nutritional status, 103
migration, 45, 64
mimicry, 72
mind-body, 163 O
mitogen, 147
models, 30, 108, 111, 112, 116, 126, 130 obesity, 6
moisture, 28, 35 obstruction, 151
molecules, 67, 119, 122, 147 oil, 69
Montenegro, iii, v, vii, 185, 195 old age, 197
morbidity, 108, 179, 204 oophorectomy, 25, 27
morphine, 33, 34 opacity, 55
morphology, 194, 197, 199, 204 operations, 67
mortality, 205 opioids, 26, 27, 32, 33, 34, 35, 136, 162
mortality rate, 205 opportunities, 1, 104
motor fiber, 115 organ, 13, 18, 19, 38, 86, 98, 108, 115, 116, 120,
myalgia, 76, 100, 109, 142, 172 123, 124, 125, 126, 127, 131, 135, 152, 172, 178
myositis, 15 organic compounds, 47
organism, 88, 160
organs, 15, 16, 18, 21, 24, 26, 47, 84, 85, 86, 94,
N 108, 109, 110, 114, 115, 116, 117, 118, 131, 132,
140, 141, 213
Na+, 120 orgasm, 155, 175
narratives, 180 ossification, 45
nausea, 26, 132, 133 osteoporosis, 25
necrosis, 21, 26, 139, 140 osteotomy, 201, 207
negative influences, 155 ovarian cancer, 135
neural development, 126 ovarian cysts, 25, 88, 130, 181
neural network, 46 ovariectomy, 111, 118, 120
neuralgia, 10, 17, 37, 41 ovaries, 23, 108, 110, 130
neurogenic bladder, 116 overlap, 51, 80, 97, 108, 110, 111, 119, 124, 131,
neurokinin, 117, 138 141, 178
neuroleptics, 190 ovulation, 19, 23, 132, 144
neuroma, 3 oxalate, 28
neuromuscular diseases, 49 oxygen, 44, 65
Index 229
plantar flexion, 50
P plasma levels, 133
plasticity, 118
pallor, 13
playing, 15, 34
palpation, 5, 6, 8, 11, 12, 13, 77, 81, 83, 90, 91, 93,
plexus, 2, 3, 6, 7, 8, 16, 79, 122, 177
157, 175, 188, 191, 195
pneumothorax, 190
palpitations, 30
Poland, 43
pancreas, 16
pollen, 162, 169
parallel, 200
polymorphisms, 153, 168
paralysis, 37
polyp, 22
parasitic infection, 188
polyps, 18, 22
parenchyma, 159
population, 37, 122, 152, 167, 171, 172, 179, 198,
paresthesias, 6
206
partial seizure, 30
potassium, 88, 124, 180
participants, 209, 211
precipitation, 141
pathogenesis, 71, 74, 92, 110, 112, 120, 124, 126,
precursor cells, 45
130, 134, 135, 137, 140, 143, 149, 159, 161, 164,
prednisone, 161
178
pregnancy, 18, 19, 38, 113, 147
pathology, 68, 76, 90, 111, 112, 142, 151, 175, 176,
prematurity, 20
186, 189, 204, 210
prevention, 148, 161, 182, 183
pathophysiological, 27, 133
primary dysmenorrhea, 133, 144
pathophysiology, 1, 27, 121, 127, 133, 149, 160, 179
primate, 111
pathways, 34, 45, 108, 112, 113, 115, 116, 117, 119,
probability, 65, 66
120, 126, 153, 160
probe, 215
pectineus, 96
proctitis, 84, 94
penis, 12, 79, 80, 81, 82, 90
prodrugs, 51
percentile, 213, 215
professionals, 76, 93, 94, 152, 165
perforation, 20
progesterone, 25, 114, 117, 133, 136, 139, 140
perfusion, 190
prognosis, 98, 132, 150
perineum, 2, 3, 8, 10, 16, 34, 78, 79, 80, 81, 153,
prolactin, 103
155, 157, 159, 210, 211, 213, 215
prolapse, 88
periosteum, 132
proliferation, 22, 45, 46, 65, 67, 120, 148, 161, 173
peristalsis, 134
promoter, 153
peritoneal cavity, 20, 22, 23
propagation, 113, 116
peritoneum, 23, 26, 110, 130, 135, 138, 139
prostaglandins, 23, 135, 139, 144, 188
peritonitis, 19, 22, 23, 135
prostate cancer, 153, 154, 161, 169
permeability, 113, 118, 121
prostate gland, 151, 159
permeation, 46, 47
prostatitis, 76, 77, 84, 89, 94, 99, 100, 104, 105, 124,
permit, 190, 192
149, 150, 151, 152, 153, 154, 157, 158, 159, 161,
pharmacology, 194
163, 165, 166, 167, 168, 169, 210, 216
pharmacotherapy, 51, 176
prostatodynia, 77, 149, 150, 165, 166
phenol, 32, 177
protein kinases, 147
phenotype, 118, 122, 164
proteins, 117, 147
phenotypes, 108, 110
proteoglycans, 66, 73
Philadelphia, 100, 101, 103, 107, 168
proteolytic enzyme, 65
phosphorylation, 124
prototype, 55
photographs, 176
psychological distress, 111
physicians, 97, 160, 164, 188
psychosomatic, 136, 142, 193
physiology, 103
puberty, 198
physiopathology, vii, 85, 152, 213
pubis, 2, 8, 10, 79, 81, 198
piloerection, 187
public health, 210
pilot study, 39, 95, 102, 143, 144, 148, 160, 181,
pumps, 33
182, 206
pus, 64
placebo, 102, 104, 160, 161, 162, 163, 167, 169, 180
230 Index
pyrophosphate, 70 115, 116, 117, 118, 119, 123, 124, 139, 153, 156,
159, 160, 162, 168, 182, 188, 189, 192
restoration, 141
Q restrictions, 96
reticulum, 188
quality of life, 1, 30, 31, 36, 68, 72, 84, 95, 98, 105,
rheumatoid arthritis, 151
107, 119, 129, 130, 142, 143, 154, 155, 156, 158, rhythm, 95
161, 162, 172, 174, 175, 178, 179, 180, 193, 215
rings, 47
quantification, 194
room temperature, 46
questionnaire, 53, 90, 141, 151, 156, 171 root, 67, 73, 79, 101, 103, 115, 116, 117, 120, 121,
122, 123, 124, 125, 138, 195
R
S
radiation, 7, 15, 141, 174, 175, 211
radiculopathy, 71, 103 sacrum, 18, 83, 198, 201, 202
radio, 34 safety, 95, 102, 167
rating scale, 174 salpingitis, 22, 89, 129, 137
reactions, 45, 65, 67, 88, 192 sample mean, 212
reactivity, 72 scar tissue, 3
reading, 84, 210 sciatica, 17, 68
receptors, 2, 14, 15, 18, 46, 52, 53, 113, 117, 118, science, 108, 116, 123, 207
122, 126, 133, 138, 139, 140, 144, 153 sclerosis, 173
recognition, 140 scoliosis, 68, 69, 87, 188
recommendations, 156, 165, 182, 193 scrotum, 78
reconstruction, 45 secrete, 136
recovery, 58, 67, 87, 93 secretion, 25, 71, 117, 126, 152, 158, 168
rectum, 3, 8, 15, 16, 17, 36, 41, 81, 85, 114, 183 sediment, 150
rectus abdominis, 3 seizure, 4
recurrence, 25, 35, 141, 142, 148, 173, 178, 182 selective serotonin reuptake inhibitor, 30, 176
reflexes, 4, 5, 7, 9, 13, 14, 50, 86, 115, 195 self-esteem, 155
regeneration, 65, 71 semen, 79, 150, 159, 210, 211
regression, 63, 209, 212 sensation, 4, 5, 8, 9, 10, 12, 13, 17, 53, 55, 68, 81,
rehabilitation, 31, 40, 96, 177, 201 113, 124, 129, 133, 135, 140, 153
rehabilitation program, 177 sensations, 9, 14, 53, 108, 115
relaxation, 28, 44, 76, 95, 96, 97, 98, 99, 163 senses, 14
relevance, 70, 130, 143, 150, 181 sensitivity, 2, 3, 8, 11, 14, 15, 34, 37, 53, 54, 86, 105,
reliability, 189, 191, 212, 214 112, 113, 114, 116, 120, 121, 124, 125, 162, 175,
relief, 7, 11, 27, 29, 30, 31, 32, 34, 40, 48, 64, 95, 180, 189, 191
102, 136, 142, 161, 162, 163, 176, 178 sensitization, 76, 85, 86, 87, 99, 108, 113, 114, 116,
remission, 40, 46, 65, 67, 125 119, 120, 123, 124, 125, 126, 137, 152, 164, 169,
remodelling, 138 210, 211, 216
repair, 3, 64 sensors, 14, 15
reproductive age, vii, 23, 129, 130, 185, 186 sensory modality, 108
reproductive organs, 108, 118, 130, 132 sepsis, 157
requirements, 103 septum, 18, 20, 23, 24, 110, 131, 135, 137, 192
researchers, 45, 134, 210, 214 serotonin, 88, 117, 137, 139, 162, 188
resection, 20, 21, 22, 34, 45, 163, 207 serum, 55, 89, 103, 158
resistance, 17, 25, 45, 97, 133 services, 1, 187
resolution, 72, 95 shape, 20, 92, 206
resources, 1, 192 shock, 20, 99, 163, 169
respiratory problems, 204 showing, 52, 54, 56, 159, 185, 192
response, 10, 13, 14, 19, 22, 28, 29, 30, 32, 33, 52, side effects, 63, 95, 141, 164
64, 67, 77, 78, 83, 88, 91, 93, 94, 99, 101, 110, sigmoid colon, 110
Index 231
signalling, 53, 117, 127 stress factors, 163

signals, 32, 33, 215 stressors, 17
signs, 9, 12, 13, 23, 24, 26, 70, 72, 98, 150, 194 stretching, 9, 28, 83, 95, 96, 163
skeletal muscle, 159, 160, 187 stroma, 109, 152, 165, 173
skin, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 23, stromal cells, 131, 139
28, 29, 35, 46, 47, 49, 51, 52, 53, 54, 58, 60, 61, structural changes, 111
62, 78, 85, 86, 115, 118, 120, 132, 190, 209, 211, structure, 44, 45, 46, 47, 51, 63, 64, 65, 66, 108, 116,
214, 215 147
sleep disturbance, 172 subcutaneous tissue, 15, 93
smoking, 84 subgroups, 210
smooth muscle, 114, 123, 129, 134, 139, 145, 147, substrate, 44, 45
152, 161 subtraction, 207
smooth muscle cells, 129, 134, 139, 147, 152 success rate, 192
SNS, 17 sulfate, 113
social stress, 136 Sun, 146
Socrates, 76 supplementation, 122, 127
sodium, 73, 167 suppression, 65, 134, 142
software, 49, 211 suprapubic, 4, 78, 113, 157
solution, 51, 52 surface area, 44, 48, 63
somatic nervous system, 17 surgical intervention, 201, 204
spam, 31 surgical removal, 137
spastic, 31 surgical resection, 34
specialists, 75, 164 surgical technique, 34, 204
speculation, 152 surveillance, 45
sperm, 145 survival, 117, 124
sphincter, 14, 35, 78, 79, 80, 81, 85, 95, 152, 165, susceptibility, 9
209, 211, 215, 217 suture, 3
spin, 66 sweat, 47
spinal cord, 33, 34, 64, 86, 111, 115, 116, 117, 124, swelling, 46, 78
163, 173, 188 symmetry, 44, 52, 54, 58, 63, 69, 91, 187
spinal stenosis, 207 sympathetic fibers, 173
spine, 4, 5, 6, 11, 12, 15, 36, 44, 46, 49, 53, 67, 73,
80, 98, 102, 187, 197, 198, 201, 203, 204, 205,
206, 207 T
spondylolisthesis, 206
Spring, 37, 40 T cell, 73, 118
sprouting, 135, 138, 139 Taiwan, 100, 194
squamous cell, 10 tamoxifen, 126
squamous cell carcinoma, 10 target, 103, 108, 115, 176, 177
stability, 198, 211, 212 target organs, 115
stabilizers, 27 technician, 214
standard deviation, 198 techniques, 28, 31, 35, 66, 76, 95, 98, 195, 205, 215
standardization, 149 teenage girls, 129
stasis, 21 temperature, 6, 32, 46, 47, 51, 78, 92, 187
state, 21, 44, 85, 86, 153, 177 tendinitis, 94
steel, 190 tendon, 7, 9, 92
stenosis, 18, 20, 35, 131 tendons, 15
sterile, 211 tension, 75, 76, 84, 85, 87, 91, 97, 98, 133, 163, 172,
steroids, 94, 119 186, 187, 188, 189
stimulus, 13, 46, 64, 86, 108, 115, 116, 166, 171, 187 terminals, 72
stomach, 82 terpenes, 47
stratification, 44 territory, 12
stress, 27, 84, 85, 90, 98, 120, 154, 163, 174, 195 testing, 34, 36, 37, 108, 210
texture, 91
232 Index
thalamus, 85, 86 tumor growth, 21

therapeutic approaches, 108, 119 tumor necrosis factor, 152
therapeutic interventions, 92 tumors, 26, 136
therapeutic targets, 111 tumours, 203
therapeutic use, 97, 136 twins, 101
therapist, 215, 217
therapy, 23, 25, 27, 28, 31, 32, 33, 35, 40, 47, 49, 65,
68, 93, 94, 95, 97, 101, 102, 105, 108, 130, 136, U
138, 142, 146, 151, 156, 160, 161, 162, 163, 164,
167, 168, 169, 176, 177, 178, 179, 182, 183, 190, ulcer, 17
193, 195, 204 ultrasonography, 175, 181
threshold level, 61 ultrasound, 21, 22, 24, 26, 32, 38, 47, 93, 95, 123,
thrombosis, 19, 26, 39 141, 165, 175, 181, 195
thyroid, 103, 188 underlying mechanisms, 107, 111, 116
thyrotropin, 103 urban, 104
tin, 13, 107 urban population, 104
tinnitus, 30 ureter, 5, 15, 131
tissue, 1, 19, 22, 23, 26, 34, 44, 45, 47, 64, 65, 70, ureters, 110
72, 73, 92, 97, 99, 110, 111, 112, 113, 114, 115, urethra, 3, 8, 16, 34, 78, 79, 80, 82, 85, 90, 114, 116,
121, 130, 137, 141, 146, 148, 153, 167, 172, 173, 124, 152, 153, 155, 191
177, 189 urethral syndrome, 97, 107, 124
tonic, 112, 192 urethritis, 84, 94, 124
torsion, 19, 21, 25, 26, 27 urinalysis, 155
toxicity, 89 urinary bladder, 110, 116, 117, 118, 120, 121, 123,
toxin, 33, 35, 41, 76, 94, 95, 100, 101, 102, 104, 162, 124, 125, 126, 127, 130
166, 192, 195 urinary dysfunction, 98, 163, 174
trace elements, 88 urinary retention, 157
training, 28, 76, 84, 99, 215 urinary tract, 84, 104, 108, 109, 111, 112, 117, 121,
traits, 30, 174 122, 127, 150, 153, 155, 156, 166, 173, 210
transcription, 117 urine, 79, 113, 117, 120, 123, 150, 151, 154, 155,
transection, 177 157, 158, 159, 161, 210, 211
transformation, 110 uroflowmetry, 211
transforming growth factor, 139, 148 urologist, 167
translation, 181, 217 urothelium, 117, 118, 121, 125
transmission, 28, 33, 34, 88, 95, 108, 116, 119, 137, uterine fibroids, 38, 145
142 uterus, 2, 5, 18, 19, 20, 21, 23, 38, 108, 109, 110,
transplantation, 3, 23 114, 116, 121, 122, 124, 130, 134, 135, 140, 145,
transport, 110, 145 147, 173
transurethral resection, 105
transverse colon, 16 V
transversus abdominis, 4
trauma, 2, 3, 5, 10, 11, 17, 25, 77, 84, 93, 98, 190, vacuum, 64, 65, 66, 72
191, 201 vagina, 3, 8, 15, 16, 20, 21, 22, 34, 36, 78, 85, 108,
trial, 31, 38, 40, 41, 105, 161, 162, 166, 167, 168, 110, 114, 121, 131, 137, 173
176, 178, 180, 183 vaginitis, 84, 94
tricyclic antidepressant, 29, 30, 40, 162, 166, 176 vagus, 111
tricyclic antidepressants, 29, 30, 40, 166, 176 vagus nerve, 111
trigeminal neuralgia, 31 validation, 159, 166, 181, 216, 217
triggers, 104, 122, 126 variables, 142, 217
trochanter, 18 variations, 70, 99, 121, 151
tubal ligation, 23 vascular endothelial growth factor (VEGF), 139
tuberculosis, 211 vascular surgery, 3
tumor, 21, 27, 132, 152 vascular system, 64, 115
uploaded by [stormrg]
Index 233
vascularization, 21
vasculature, 19 W
vasoactive intestinal peptide, 139
walking, 6, 10, 27, 200
vasoconstriction, 133, 153, 187
Washington, 165
vasodilation, 116, 117
water, 28, 44, 85, 88, 89, 211
vasopressin, 133, 144, 145
weakness, 5, 8, 30, 31, 35, 77, 83, 90, 187
vasovagal syncope, 190
wear, 28
vector, 63
web, 64
vegetable oil, 28
weight control, 28
vein, 19, 26, 39
weight gain, 133
vertebrae, 198, 202
welfare, 28
vesicle, 47
white blood cell count, 158
vessels, 20, 21, 27, 64, 67, 138, 146
wild type, 118
vibration, 47
withdrawal, 114
viral gene, 117
workers, 49, 154, 155
viscera, 18, 78, 84, 85, 98, 110, 114, 115, 120
World Health Organization (WHO), 27
vision, 36
worldwide, 171, 210
visualization, 25, 36, 129, 175
wound dehiscence, 35
vitamin A, 89
vitamin C deficiency, 88
vitamins, 88, 89 Y
voiding, 149, 150, 155, 156, 161, 163, 210
vomiting, 26 yeast, 112
vulva, 8, 10, 11, 13, 16, 28, 36, 108, 115, 191 young women, 21, 26, 172
vulvodynia, 9, 10, 11, 29, 30, 31, 37, 39, 40, 77, 107,
111, 112, 119, 121, 122, 126

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Human Anatomy and Physiology

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Pain and its Origins, Diagnosis and

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MARY LOURDES LIMA DE SOUZA MONTENEGRO

Nova Biomedical Books

NOTICE TO THE READER

Library of Congress Cataloging-in-Publication Data

Published by Nova Science Publishers, Inc. New York

Chapter X Skin Surface Electromyography in Chronic Prostatitis

Mary Lourdes Montenegro

Augusto Pereira-Sanchez, Tirso Perez-Medina,

Neuropathic pain results from injury of peripheral or central nervous system.

Sharp, intense, shocking or penetrating pain.

Nociceptive pain is caused by stimulation of nociceptive receptors. The characteristics of

Muted or intense pain.

I. Neuropathic Pain in Gynecology

Peripheral Nervous System (PNS) [3]

a) Perineal Sensitivity at Lumbar Plexus

Table 1. Lumbar nerves and innervations area

b) Perineal Sensitivity at Sacral Plexus

Table 2. Sacral nerves and innervations area

Lumbar Neuralgia [4, 5]

Causes of Neuropathy in the Lumbar Region

Direct surgical trauma.

b) Nerve ischemia: interruption of blood flow supply at intrapelvic vascular surgery,

A. Iliohypogastric Neuralgia [6]

Inguinal herniorrhaphy and appendectomy.

Location: lower abdominal incisions (Pfannenstiel)

Tactile surface exploration

Lower abdominal skin reflexes

B. Ilioinguinal Neuralgia [6]

Inguinal hernia repair or appendectomy.

Location: Compression of ilioinguinal nerve as it passes through transversus abdominis

Tactile surface exploration

Lower abdominal skin reflexes (see above)

C. Genitofemoral Neuralgia [6,7]

Inguinal hernia repair or appendectomy.

Tactile surface exploration

Positive Q-tip test with the application of light.

Geigel reflex (cremasteric reflex in male) (L1-L2)

Friction inner thigh and contraction of the external oblique muscle.

D. Lateral Femoral Cutaneous Neuralgia or Meralgia Paraesthetica [6]

Cause: The nerve can be injured by:

Trauma or penetrating wounds of the thigh.

Tactile surface exploration: not supported some clothes and a belt

Q-tip test: hyperesthesia or dysesthesia in the corresponding area, sometimes find an

Reflexes: Lateral femoral cutaneous nerve is exclusively sensitive. There is no motor

Differential diagnosis of cutaneous nerves

History of a surgical procedure in the lower abdomen.

In patients with persistent pain and paresthesia in the inguinal region

1. Ilioinguinal nerve block: assessing symptom relief

E. Obturator Neuralgia [8]

Clinic and physical exploration

Tactile surface exploration

Loss of sensation in the mid inner thigh.

Posterior Femoral Cutaneous Neuralgia

Clinic and physical exploration

Tactile surface exploration

Tinel's sign positive when palpation of the posterolateral thigh.

Anatomy of pudendal nerve

B.1. Vulvodynia [9,10]