The Journal of Pain, Vol 10, No 11 (November), 2009: pp 1170-1178

Available online at www.sciencedirect.com

Bilateral Widespread Mechanical Pain Sensitivity in Women With

Myofascial Temporomandibular Disorder: Evidence of Impairment
in Central Nociceptive Processing

César Fernández-de-las-Peñas,*yz Fernando Galán-del-Rı́o,*y Josué Fernández-Carnero,*y

Jorge Pesquera,x Lars Arendt-Nielsen,z and Peter Svensson{#s
* Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan
Carlos, Alcorcón, Madrid, Spain.
y
Esthesiology Laboratory of Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
z
Centre for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University,
Aalborg, Denmark.
x
Dental and Orofacial Pain Department, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
{
Department of Clinical Oral Physiology, School of Dentistry, University of Aarhus, Aarhus, Denmark.
#
Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark.
s
Orofacial Pain Laboratory, Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark.

Abstract: Our aim was to investigate bilateral, widespread pressure-pain hypersensitivity in nerve,
muscle, and joint tissues in women with myofascial temporomandibular disorders (TMD) without
concomitant comorbid conditions. Twenty women with myofascial TMD (aged 20 to 28 years old),
and 20 healthy matched women (aged 20 to 29 years), were recruited. Pressure-pain thresholds
(PPT) were bilaterally assessed over supra-orbital (V1), infra-orbital (V2), mental (V3) nerves, median
(C5), radial (C6) and ulnar (C7) nerve trunks, the C5-C6 zygapophyseal joint, the lateral pole of the
temporo mandibular joint (TMJ), and the tibialis anterior muscle in a blinded design. The results
showed that PPTs were significantly decreased bilaterally over the supra-orbital, infra-orbital, and
mental nerves, median, ulnar, and radial nerve trunks, the lateral pole of the TMJ, the C5-C6 zygapo-
physeal joint, and the tibialis anterior muscle in patients with myofascial TMD as compared to
healthy controls (all sites: P < .001). There were no significant differences in the magnitude of PPT
decreases between the trigeminal and extratrigeminal test sites. PPT over the mental nerve, the
TMJ, C5-C6 zygapophyseal joint and tibialis anterior muscle were negatively correlated to both dura-
tion of pain symptoms and TMD pain intensity (P < .05). Our findings revealed bilateral, widespread
pressure hypersensitivity in women presenting with myofascial TMD, suggesting that widespread
central sensitization is involved in myofascial TMD women.
Perspective: This article reveals the presence of bilateral and widespread pressure-pain hypersen-
sitivity in women with myofascial TMD, suggesting that widespread central sensitization is involved
in myofascial TMD. This finding has implications for development of management strategies.
ª 2009 by the American Pain Society
Key words: Temporomandibular disorder, pressure-pain threshold, central sensitization.

T
emporomandibular disorder (TMD) is a term debate, but studies have shown prevalence rates
including different conditions involving the between 3 and 15% in the Western population,27 with
temporomandibular joint (TMJ) and the mastica- an incidence between 2 and 4%.13 A recent survey
tory muscles. The lifetime prevalence of TMD is under determined that the overall prevalence of TMD pain
was 4.6%, with 6.3% for women and 2.8% for men.24
Received February 9, 2009; Revised March 18, 2009; Accepted April 20, Further, myofascial TMD is considered as prevalent as
2009.
Address reprint requests to César Fernández de las Peñas, Facultad tension-type headache.51
de Ciencias de la Salud, Universidad Rey Juan Carlos, Avenida de Atenas TMD is often found in conjunction with other wide-
s/n, 28922 Alcorcón, Madrid, Spain. E-mail: cesar.fernandez@urjc.es
1526-5900/$36.00
spread pain syndromes, such as fibromyalgia.56 Further,
ª 2009 by the American Pain Society pain outside the masticatory system (widespread pain)
doi:10.1016/j.jpain.2009.04.017 has been shown to be a significant risk factor for onset

1170
Fernández-de-las-Peñas et al
52
of dysfunctional TMD pain among women. Therefore,
it has been suggested that a generalized hyperexcitabil-
ity in the central processing of nociceptive input is impli-
cated in the pathophysiology of TMD.37
Pressure-pain thresholds (PPT)7,35 have been exten-
sively used for investigating mechanical-pain sensitivity
in several pain conditions, eg, whiplash,45 fibromyal-
gia,10 repetitive strain injury,21 tension-type headache,16
low back pain,32 and osteoarthritis.2 All these studies
have consistently showed lower PPT levels in both local
painful and distant pain-free areas, suggesting that
widespread pressure-pain hyperalgesia may reflect gen-
eralized hyperexcitability of the second-order (or higher)
nociceptive neurons in the central nervous system.
Previous studies investigating PPT in patients with
TMD have, however, shown conflicting results. Farella
et al15 and Reid et al34 found lower PPTs in both masseter
and temporalis muscles in TMD patients. Maixner et al29
and Kashima et al26 showed lower PPT levels in the mas-
ticatory muscles and in the arm (nontrigeminal region) in
myofascial TMD patients. Svensson et al47 reported that
PPTs were also lower in the tibialis anterior muscle in
TMD patients. On the contrary, other studies did not
show significant differences on PPTs in the index finger
between TMD patients and healthy controls.6,46 These
conflicting results may be attributable to a small sample
size46 or differences between the patient groups.6 Fur-
thermore, TMD patients included in the study by Carlson
et al6 showed significant levels of anxiety and depres-
sion, which are known to affect pain sensitivity. There-
fore, studies with homogeneous sample sizes with
lower levels of depression and anxiety are needed.
In addition, these studies evaluated PPT levels in deep
tissues, particularly the muscles. Recent studies have
investigated pressure-pain sensitivity over nerve trunks
in patients with whiplash,40 or chronic tension-type
headache.17 To the best of the authors’ knowledge,
no published studies have previously investigated
pressure-pain hypersensitivity over nerve trunks in myo-
fascial TMD patients. In order to investigate the presence
of central nociceptive impairment in patients with myo-
fascial TMD, we also assessed the presence of widespread
mechanical-pain sensitivity. Therefore, the aim of our
study was to investigate bilateral widespread pressure-
pain hyperalgesia in nerve, muscle, and joint tissues in
women with myofascial TMD.
Methods
Subjects
Patients diagnosed with TMD by an experienced den-
tist from the Specialist Centre for TMD Treatment, Uni-
versidad Rey Juan Carlos, were screened for eligibility
criteria. Women diagnosed with myofascial TMD accord-
ing to the Research Diagnostic Criteria for TMD (RDC/
TMD) were included.14 In addition, patients should
have presented spontaneous pain involving the masseter
muscle with a duration of at least 6 months and an inten-
sity of at least 3 on an 11-point numerical pain rating
scale (NPRS). The following signs/symptoms were as-
sessed using the RDC/TMD diagnostic criteria: location
1171
of pain, jaw range of motion and associated pain, TMJ
sounds, and pain upon muscle and joint palpation.14 An
11-point NPRS25 (0 = no pain; 10 = maximum pain) was
used to assess current level of pain, worst, and lowest
level of pain experienced in the preceding week. The
Beck Depression Inventory (BDI-II), a 21-item self-report
measure assessing affective, cognitive, and somatic symp-
toms of depression, was also used.4 The BDI-II has shown
good internal consistency (a = .86), with higher scores
indicating higher levels of depressive symptoms.3
TMD patients were excluded if they exhibited any of
the following criteria: 1) other concomitant diagnosis ac-
cording to the RDC/TMD criteria; 2) younger than 18 or
older than 65 years old; 3) previous interventions with
surgery and/or steroid injections; 4) fibromyalgia55; 5)
diagnosis of systemic disease (rheumatoid arthritis,
systemic lupus erythematosus, or psoriatic arthritis); 6)
previous cervical or head trauma (whiplash); 7) preg-
nancy; 8) presence of a score>9 points in the BDI-II; and
9) concomitant diagnosis of any primary headache (ten-
sion-type headache or migraine).
Finally, healthy controls were recruited from volun-
teers who responded to a local announcement and
were excluded if they exhibited a history of neck, facial
or head pain (infrequent episodic tension-type headache
was permitted), or any systemic disease or diagnosis
compatible with any TMD diagnosis according to the
RDC/TMD.
The study was supervised by the Department of Physi-
cal Therapy, Occupational Therapy, Rehabilitation and
Physical Medicine of Universidad Rey Juan Carlos, Spain.
The protocol was approved by the local Ethics Committee
(URJC 039) and conducted following the Helsinki Decla-
ration. All participants signed an informed consent prior
to their inclusion.
Pressure-Pain Threshold Assessment
Pressure-Pain Threshold (PPT) is defined as the minimal
amount of pressure where a sensation of pressure first
changes to pain.54 An electronic algometer (Somedic
Sales AB, Hörby, Sweden) was used to measure PPT
(kPa). The pressure was applied at a rate of 30 kPa/sec-
ond. All participants were instructed to press switch
when the sensation changed from pressure to pain.
The mean of 3 trials (intra-examiner reliability) was calcu-
lated and used for the analysis. A 30-second resting pe-
riod was allowed between each measure. The reliability
of pressure algometry has been found to be high (ICC =
.91 [95% CI .82 - .97]).8
Sample-Size Determination
The sample size determination and power calculations
were performed with an appropriate software (Tamaño
de la Muestra, 1.1, Madrid, Spain). The calculations
were based on detecting, at a minimum, significant clin-
ical differences of 20% on PPT levels between both
groups57 with an alpha level of .05, and a desired power
of 80% and an estimated interindividual coefficient of
variation for PPT measures of 20%. This generated a sam-
ple size of at least 16 participants per group.
1172
Study Protocol
The study protocol was the same for patients and con-
trols. All examinations were performed in a quiet, draft-
free, temperature- and humidity-controlled laboratory
(24 C 6 1 C, relative humidity 25-35%). All participants
had abstained from vigorous exercise from the previous
day. None of the patients were taking any preventive
drug or oral contraceptives at the time the study was per-
formed. Participants were not allowed to take analgesics
or muscle relaxants through the 72hours prior to the ex-
amination. Women were not tested in any particular
phase of their menstrual cycle due the minor effect of
menstrual cycle on pressure-pain sensitivity.5 PPT levels
were measured bilaterally over supra-orbital (V1), infra-
orbital (V2), mental (V3), median (C5), ulnar (C7) and
radial (C6) nerves, the articular pillar of C5-C6 zygapo-
physeal joint, the lateral pole of the TMJ, and the tibialis
anterior muscle by an investigator blinded to the sub-
jects’ condition. The order of assessment was random-
ized between the participants.
All nerve-trunk nerves were identified by manual pal-
pation and marked with a pencil. The supra-orbital nerve
(V1) was located over the supra-orbital foramen (at the
junction between the lateral and medial third of the
upper part of the margin of the orbit), the infra-orbital
nerve (V2) was located over the infra-orbital foramen
above the canine fossa, and the mental nerve from the
mandibulary nerve (V3) was located over the mental
foramen on the anterior surface of the mandible.
The median nerve (C5) was located over the cubital
fossa medial to and adjacent to the tendon of biceps,
the ulnar nerve (C7) was located in the groove between
the medial epicondyle and the olecranon, and the radial
(C6) nerve was marked where it passes through the lat-
eral intermuscular septum between the medial and lat-
eral heads of triceps to enter the mid to lower third of
the humerus.
Finally, the articular pillar of the C5-C6 zygapophyseal
joint, the lateral pole of the TMJ, and the tibialis anterior
were located as in previous studies.10,40,45
Pressure-Pain Threshold Data
Management
In the current study, the magnitude of sensitization
was investigated, assessing the differences of absolute
and relative PPT values between both groups. For rela-
tive values, we calculated a PPT index dividing the PPT
of each patient at each point by the mean of PPT score
of the control group at the same point.
Statistical Analysis
Data were analyzed with the SPSS statistical package
(SPSS v.14.0; SPSS, Inc., Chicago, IL). Results are expressed
as mean and 95% confidence interval (95% CI). The Kol-
mogorov-Smirnov test was used to analyze the normal
distribution of the variables (P > .05). Quantitative data
without a normal distribution (ie, pain history, current
level of pain, least and worst level of pain in the preced-
ing week) were analyzed with nonparametric tests,
whereas data with a normal distribution (PPTs) were
Pressure Pain Sensitivity in TMD
analyzed with parametric tests. The intraclass correlation
coefficient (ICC) was used to assess intra-examiner reli-
ability of PPT data. A 2-way ANOVA test was used to in-
vestigate the differences in PPT assessed over each
point (supra-orbital, infra-orbital, mental, median, ra-
dial, and ulnar nerves, the lateral pole of the TMJ, the
C5-C6 joint and the tibialis anterior muscle) with side
(most affected/contra-lateral or dominant/nondomi-
nant) as within-subject factor and group (patients or
controls) as the between-subject factor. A 2-way ANOVA
test was also used for assessing differences in PPT Index
with side (most affected/contra-lateral or dominant/non-
dominant) as within-patient factor and point (supra-or-
bital, infra-orbital, mental, median, radial, and ulnar
nerves, the lateral pole of the TMJ, the C5-C6 zygapophy-
seal joint, and the tibialis anterior) as between-patient
factor. Post hoc comparisons were done with the Tukey
test. Finally, the Spearman’s rho (rs) test was used to ana-
lyze the association between PPTs and the clinical vari-
ables relating to symptoms. The statistical analysis was
conducted at a 95% confidence level, and a P value less
than .05 was considered statistically significant.
Results
Demographic and Clinical Data of the
Patients
Fifty-two consecutive patients presenting with TMD
between December, 2007 and November, 2008 were
screened for possible eligibility criteria. Thirty-two pa-
tients were excluded for the following reasons: concom-
itant diagnosis of arthralgia according to the RDC/TMD
(n = 9), concomitant migraine (n = 8), previous whiplash
injury (n = 8) and concomitant diagnosis of fibromyalgia
(n = 7). Finally, a total of 20 women presenting with my-
ofascial TMD, aged 20 to 28 years old (mean: 23 6 3 years)
satisfied all the inclusion criteria and agreed to partici-
pate. In addition, 20 matched healthy women without
TMD, aged 20 to 29 years old (mean: 23 6 3 years) also
participated (P = .813). All patients reported bilateral
symptoms; nevertheless, 8 of them (40%) reported their
right side as the most affected, and the remaining 14
(60%) the left side. The mean duration of TMD pain
was 22.8 months (95% CI 14.9-30.8 months). The mean
current level of pain was 4.0 (95% CI 3.4-4.6), the worst
level of pain experienced in the preceding week was
6.5 (95% CI 6.1-6.9), and the lowest level of pain in the
preceding week was 1.9 (95% CI 1.5-2.2).
Further, positive correlations between duration-of-
pain history and lowest level of pain (rs = .52; P = .02)
and worst level of pain experienced in the preceding
week (rs = .42; P = .045) were found: the longer the dura-
tion of the symptoms, the greater the intensity of the
perceived pain (Fig 1).
Pressure-Pain Sensitivity Over Trigeminal
Nerve Trunks
The intra-examiner repeatability of PPTreadings for the
trigeminal nerve ranged from .89 to .92 for the most pain-
ful side and from .90 to .92 for the contra-lateral side. The
Fernández-de-las-Peñas et al 1173

Figure 1. Scatter plots of relationships between duration of temporomandibular disorder (TMD) pain and numerical pain rating
scale (NPRS) values (n = 20). Note that some points are overlapping. A positive linear regression line is fitted to the data.

standard error of measurement (SEM) ranged from 5.3 to
5.9 kPa for the most painful side and from 5.8 to 6.2 kPa
for the contra-lateral side.
The ANOVA revealed significant differences between
both groups, but not between sides, for PPT levels over
the supra-orbital (group: F = 262.9; P < .001; side: F =
.08; P = .771), infra-orbital (group: F = 273.8; P < .001;
side: F = .08 P = .847) and mental (group: F = 289.7;
P < .001; side: F = .01; P = .977) nerves. Over each nerve,
patients showed bilateral lower PPT levels than healthy
controls (P < .001). Table 1 summarizes PPT assessed over
supra-orbital (V1), infra-orbital (V2) and mental (V3)
nerve for both sides within each study group.
Pressure-Pain Sensitivity Over Peripheral
Nerve Trunks
The intra-examiner repeatability of PPTreadings for the
3 nerve trunks ranged from .91 to .95 for the most painful
side and from .90 to .93 for the contra-lateral side. The
SEM ranged from 6.1 to 6.4 kPa for the most painful
side and from 5.9 to 6.2 kPa for the contra-lateral side.
The ANOVA revealed significant differences between
both groups, but not between sides, for PPT levels over
the median (group: F = 300.4; P < .001; side: F = 0.2;
P = .635), radial (group: F = 437.3; P < .001; side: F = 0.01
P = .918) and ulnar (group: F = 484.6; P < .001; side: F =
1.2; P = .301) nerves. Over each nerve, patients showed bi-
lateral lower PPT levels when compared to controls (P <
.001). Table 1 shows PPT levels over median (C5), radial
(C6), and ulnar (C7) nerve for both sides within each group.
Pressure-Pain Sensitivity Over Joints And
Muscles
The intra-examiner repeatability of PPT readings over
the C5-C6 zygapophyseal joint, the lateral pole of the
TMJ, and tibialis anterior muscle was .91, .89 and .93, re-
spectively, for the most painful side; and .90, .87 and .91
for the contra-lateral side. The SEM was 4.9, 5.4 and 6.3
kPa for the most painful side and 4.5, 6 and 6.6 kPa for
the contra-lateral side.
The ANOVA revealed significant differences between
both groups, but not between sides, for PPT levels over
the lateral pole of the TMJ (group: F = 322.3; P < .001;
side: F = .9; P = .926), the C5-C6 zygapophyseal joint
(group: F = 463.1; P < .001; side: F = 0.6; P = .432) and
the tibialis anterior muscle (group: F = 838.3; P < .001;

Pressure Pain Thresholds (PPTs) in Patients With Myofascial Temporomandibular Disorders

Table 1.
(TMD, n = 20) and Matched Control Subjects (n = 20)
TMD CONTROL

MOST PAINFUL SIDE CONTRA-LATERAL SIDE DOMINANT SIDE NONDOMINANT SIDE

Nerve
V1* 148 (134–161) 137 (124–151) 246 (232–259) 260 (246–273)
V2* 151 (133–169) 143 (125–161) 295 (277–313) 299 (281–317)
V3* 141 (122–159) 137 (119–155) 292 (274–311) 297 (279–315)
Median (C5)* 213 (191–236) 202 (180–225) 404 (381–427) 404 (381–427)
Radial (C6)* 222 (200–244) 204 (182–225) 444 (422–465) 460 (438–482)
Ulnar (C7)* 233 (213–253) 242 (222–262) 451 (431–471) 465 (445–484)
Joint
TMJ* 120 (103–138) 123 (106–141) 282 (264–299) 280 (263–298)
C5–C6* 156 (141–172) 152 (136–168) 329 (313– 345) 321 (305–337)
Muscle
Anterior tibialis* 374 (348–401) 366 (339–392) 758 (732–785) 752 (726–779)

NOTE. Mean values (kPa) and 95% confidence intervals in parentheses.

*Indicates significant difference between TMD and control subjects (ANOVA, P < .001).
1174
Figure 2. Pressure pain threshold indices in both trigeminal and extratrigeminal points. The boxes represent the mean and percen-
tile scores and the error bars represent the standard deviation.
side: F = 0.009; P = .924). Again, TMD patients showed
bilateral lower PPT in both the symptomatic and non-
symptomatic points than controls (P < .001). Table 1
summarizes PPT over the C5-C6 zygapophyseal joint,
the TMJ, and tibialis anterior muscle for both sides
within each group.
Pressure-Pain Threshold Indices
The ANOVA showed no significant differences for PPT
indices between sites (F = 2.3; P = .249) or sides (F = 1.5;
P = .521). In such a way, PPT indices were similar between
the trigeminal and extratrigeminal sites for either the
most affected or the contra-lateral side (Fig 2).
Figure 3. Scatter plot of the relationship between duration of
TMD pain and PPT levels in the tibialis anterior muscles (n = 20).
Note that some points are overlapping. A negative linear regres-
sion line is fitted to the data.
Pressure Pain Sensitivity in TMD
Pressure sensitivity and clinical features in
patients with myofascial TMD pain
Finally, significant negative correlation between dura-
tion of symptoms and PPT levels over both tibialis ante-
rior muscles (both sides, rs = –.55; P = .01, [Fig 3]) was
found: the longer the duration of the symptoms, the
lower the PPT levels. In addition, current level of pain in-
tensity was also negatively correlated with bilateral PPT
levels over the mental nerve (both sides, rs = –.47; P =
.03), the TMJ (both sides, rs = –.46; P = .04; [Fig 4A]), the
C5-C6 zygapophyseal joint (both sides, rs = –.53; P = .01
[Fig 4B]), and the tibialis anterior muscle (both sides
rs = –.47; P = .03 [Fig 4C]). In such way, the greater
the pain intensity, the lower the bilateral PPT levels.
Discussion
The main finding of the present study was a bilateral
and widespread decrease in PPT in nerve, joint, and mus-
cle tissues in myofascial TMD women when compared to
healthy controls, suggesting that central sensitization is
involved in women presenting with myofascial TMD.
The widespread decrease in PPT levels was associated
with the intensity and duration of symptoms supporting
a role of the peripheral nociceptive input in the sensitiza-
tion mechanisms.
Central Sensitization in Patients with
Myofascial TMD
In this study, PPT was significantly decreased bilaterally
over the supra-orbital, infra-orbital, mental, median, ul-
nar, and radial nerve in women with myofascial TMD as
compared to controls, suggesting both trigeminal and
extratrigeminal sensitization of afferent inputs from
neural tissues in myofascial TMD. Our results agree
with previous studies conducted in whiplash,40,45 which
showed a generalized decrease in PPTs over nerves as
sign of hyperexcitability of the central nervous system.58
Fernández-de-las-Peñas et al
Figure 4. Scatter plots of relationships between intensity of temporomandibular disorder (TMD) pain and pressure-pain threshold
(PPT) levels in the temporo mandibular joint (TMJ) joint (A); the C5-C6 zygapophyseal joint (B); and the tibialis anterior muscles (C)
(n = 20). Note that some points are overlapping. A negative linear regression line is fitted to the data.
In a sensitized state, antidromic discharges originating
from the central nervous system might sensitize periph-
eral nerve trunks,9 which may depolarize nociceptive sec-
ond-order neurons.23 An alternative explanation would
be that peripheral nociceptive nerve input is normal
but that central processing is facilitated or exaggerated.
Nevertheless, we do not exactly know what is causing the
nerve pressure pain in patients with myofascial TMD.
Consistent with a significant decrease in PPTs bilaterally
over nerve trunks, a significant bilateral decrease in PPT
levels over the lateral pole of the TMJ, the C5-C6 zygapo-
physeal joint, and the tibialis anterior muscle was also
present in our patients, suggesting multisegmental sen-
sory sensitization or sensitization of the central nervous
system in myofascial TMD women. In agreement with
our findings, previous studies have reported lower PPT
levels in the index finger and in the tibialis anterior muscle
in myofascial TMD patients.26,29,47 Additionally, myofas-
cial TMD patients have exhibited greater temporal sum-
mation to repetitive, noxious heat stimuli applied to the
palm of the hand;29 larger referred-pain areas with intra-
muscular injection of hypertonic saline into the masseter
muscle;47 increased generalized pain sensitivity after iso-
metric contraction of the orofacial muscles;31 and greater
temporal summation of pain and greater aftersensations
following repetitive, painful mechanical stimulation of
the fingers.38 Furthermore, clinical evidence consistent
with the theory that myofascial TMD is associated with
a hyperexcitability of central nervous system suggests
that these patients often report persistent pain in multiple
body areas,53 and comorbid with fibromyalgia.56
An interesting result of the current study was that the
magnitude of PPT changes between the study groups
was similar in the lateral pole of the TMJ (49.5%), the
C5-C6 zygapophyseal joint (49.8%), the tibialis anterior
muscle (49%), trigeminal nerves (49–52%), and extratri-
geminal nerve trunks (47–52%), suggesting a widespread
increased responsiveness to pressure pain in women with
myofascial TMD. These results differ from previous stud-
ies, which found that the magnitude of sensitization was
larger in the masseter (24–32%) than the anterior tibialis
1175
muscle (18%)47 or the wrist (12%).29 One possible expla-
nation is that in the current study, only women with pure
myofascial TMD were included, whereas previous studies
included both gender and some patients who fulfilled
other concomitant RDC/TMD criteria, eg, disc displace-
ment with reduction or arthralgia.29,47 Therefore, cur-
rent and previous26,29,38,47,53,56 findings suggest that
the sensitization processes are not only restricted to the
trigeminal second-order neurons, but also to extratrige-
minal nociceptive neurons, supporting the concept of
a central amplification of nociceptive inputs.
In addition to central sensitization, our results may reflect
a dysfunctional state of endogenous pain-modulatory sys-
tems, which has been previously reported in patients with
myofascial TMD5,28 Nevertheless, whether impairments in
descending inhibitory systems or central sensitization is
cause or consequence of the pain remains unknown. Recent
studies have also highlighted the importance of risk genes,
eg, polymorphisms in the gene coding for cathecol-o-
methyl-transferase, for enhanced pain sensitivity.11,12
Finally, the existence of sensitization of central ner-
vous system or impairment in descending inhibitory
mechanisms does not exclude the role of peripheral no-
ciception, since both nociceptive mechanisms are be-
lieved to be implicated in the pathophysiology of
myofascial TMD.37,50 Additionally, since central sensitiza-
tion is a dynamic condition influenced by multiple fac-
tors including the activity of peripheral nociceptive
inputs,22 it may be possible that the peripheral nocicep-
tive barrage may contribute to this process.
Peripheral Nociception Driving to Initiate
or Maintain Central Sensitization
The involvement of segmental or central sensitization has
been previously found in different local pain syndromes,
eg, repetitive-strain injury,21 chronic tension-type head-
ache,16 low back pain,32 knee osteoarthritis,2 and unilateral
shoulder pain.20 This clinical evidence is also supported by
an animal model where unilateral localized musculoskele-
tal pain caused sensitization of the contra-lateral
1176
42
segments. The existence of sensitization mechanisms in
local pain syndromes suggests that sustained peripheral,
noxious input to the central nervous system plays a role in
the initiation and maintenance of central sensitization.30
Previous studies have shown lower PPTs in the mastica-
tory muscles,15,26,29,34 as reflects of sensitization of pri-
mary nociceptive afferents in the muscle tissues. In the
current study, PPT levels over the tibialis anterior muscle,
the mental nerve, the C5-C6 zygapophyseal joint, and
the lateral pole of the TMJ were negatively associated
with pain intensity and duration of symptoms, suggest-
ing a potential role of peripheral nociceptive inputs in
the sensitization process. In fact, increased recruitment
of central neurons by peripheral nociceptive stimulation,
enhanced spatial summation,33 and spatial referral, ie,
tonic nociceptive input from local tissue, can result in
pain of remote areas, and increased pain intensity44
have been suggested to be the potential peripheral
mechanisms contributing to central sensitization pro-
cesses. However, the present study population did not
complain about musculoskeletal or pain conditions
other than myofascial TMD pain, which questions the
suggestion of peripheral sensitization from extratrigemi-
nal sites, although longitudinal studies would be re-
quired to observe if these TMD patients would also be
at risk of developing widespread pain problems.
Several experimental studies have reproduced clinical
features similar to those reported for patients with myo-
fascial TMD by injecting different algogenic substances
into the masseter muscle, eg, glutamate,49 bradykinin,1
or hypertonic saline.39 These findings support the notion
that masticatory muscles may be involved in the genesis
of myofascial TMD.48 In such instances, the initial painful
condition, that is, muscle pain (possibly induced by tissue
trauma, overload, inflammation, or ischemia) may act as
a trigger for the chronification through gradual sensiti-
zation of nociceptive pathways in myofascial TMD.
Strengths and Limitations of the Study
In the current study we included a specific group
of women diagnosed with pure myofascial TMD. We
excluded patients with other concomitant RCD/TMD
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