ANATOMY and PHYSIOLOGY

of PAIN.

Rizal Zainal
Setelahkuliah ini peserta
mampu menjelaskan.
 Apa itu nosiseptor
 Perjalanan suatu nosisepsi;
 Transduksi
 Konduksi
 Modulasi
 Transmisi
Persepsi
 Apa itu nyeri nosisepsi, Nosisepsi tanpa nyeri
Serta nyeri tanpa nosisepsi
What PAIN is?
What the textbooks would
have you believe about
pain
Noxious stimulus to the body.
Two kind of stimuli
1. Noxious stimulus (strong stimulus)
2. Innocuous stimulus ( mild stimulus)

No pain stimulus
 SSC FLC

Cortex and
Thalamus
VPL MT

Hypothalamus
and Pituitary Sympathetic
PAG Outflow

Hypothalamic-
Pituitary Outflow
Midbrain
LC

Ascending Descending
Peripheral
Pathaways Pathaways
Nociceptor

Brainstem NRM
C-Fiber Sensory
Afferent

NSTT

PSTT Delta Sensory

Afferent

Spinal Cord
Sympathetic
Efferent

A-Alpha Motor
Efferent
Nociceptive Pain is pain
that generated from
nociceptors

1. NOCICEPTORS
What is a nociceptor?
Nociceptors are peripheral sensory
neurons that respond selectively to
noxious stimuli.
,
THE BEGINNING OF INFLAMMATION PAIN
 Two distinct sensations
(dual pain sensation)
Pain intensity

early sharp, relatively brief

Aδfiber=first pain pricking sensation

C fiber=second pain
later dull, somewhat
prolonged sensation

Time

Injury
2. PERIPHERAL SENSORY
AFFERENT FIBERS
 Nerve fibers
diameter velocity
nerve fiber funtion myelin
（μ） （ｍ / ｓ）
proprioceptive
α motor 12〜20 70〜120
Tactile sense
A β 5〜12 70〜80
pressure +

γ spindle fiber 15〜80

3〜6
δ pain temperature 2〜5 12〜30
B sympatheic preganglionic 3〜15 +
＜ 3
d.r. pain 0.4〜1 0.5〜2
C －
S sympathetic postganglionic 0.3〜1.3 0.7〜2.3
 Two sensory afferent neurons
1. Large myelinated A fibers, very fast conduction velocity.
Respond to innocuous stimuli
2. Small myelinated A & C unmyelinated fibers, have slow
conduction velocity. Respond to noxious stimuli

Large
fibers A

Dorsal root
ganglion Dorsal Horn
A
Small
fibers
C Peripheral sensory
Nerve fibers
Role of nociceptors
and primary afferent
neurons are:

1. TRANSDUCTION
2. CONDUCTION
 Noxious afferent fibers
A myelinated fiber
Responds to noxious stimuli
C unmyelinated fiber
Normal Situation

Low intensity High intensity

Stimulation Stimulation

High
threshold A
 and c fiber
nociceptors

Innocuous
Brief Pain
Sensation
After Tissue Damage

Low intensity
Low threshold
stimulation
mechanorecept
or A
Sensitized
nociceptor A
and C fibers

Hyperexcitable
dorsal horn
neuron
Pain
 Neuron III Persepsion

Transduction

Mechanical Conduction
Transmission
Modulation
Neuron II
Thermal

Neuron I
Chemical
3.DORSAL HORN NEURONS
Dorsal Horn Neurons
 Is highly organized center of neurons
 The place where afferent input is processed.
 The place where terminal endings of primary
afferent ( first order neuron) and receiving
neurons (second order neurons) synapse.
 Where interaction between excitatory and
inhibitory system.
 Two types of second order nociceptive neurons
are found in DHN.
1. NS (Nociceptive-Specific Neurons
2. WDR (Wide-Dynamic Range Neuros)
4. ASCENDING PATHWAYS
 Ascending Pathways
5 ascending pathways have been recognized.
1. SPINOTHALAMIC TRACT
 Discriminative pathway  location of pain
2. SPINORETICULAR TRACT
 Emotional aspect of pain (“suffering pathway”)
3. DORSAL HORN COLUMN TRACT
 Transmission of visceral pain
4. SPINOMESENCEPHALIC TRACT
• Behavioral response
5. SPINOHYPOTHALAMIC TRACT
 Sensationl from the skin, lips & sex organs
 SSC FLC SPINOTHALAMIC TRACT
 Neo Spino Thalamic Tract direct  to
Cortex and
Thalamus Thalamus  SSC  Localizing and
VPL MT
discriminative information  withdrawal
reflex.
Hypothalamus  Pleo Spino Thalamic Tract  FLC (Frontal
and Pituitary
PAG
Sympathetic
Outflow Limbic Cortex)  Affecting circulation,
Hypothalamic- respiration, endocrine, emotional,
Midbrain
Pituitary Outflow
behavioral responses (fear, anxiety,
LC
helplessness, avoidance).

Ascending Descending
Peripheral
Pathaways Pathaways
Nociceptor

Brainstem NRM
C-Fiber Sensory
Afferent

NSTT

PSTT Delta Sensory

Afferent

Spinal Cord
Sympathetic
Efferent

A-Alpha Motor
Efferent
5.DESCENDING MODULATING
PATHWAYS
 Descending Modulating
Pathways
Those ascending pathways is modulated by descending
modulating pathways in several higher centers;

 CEREBRAL CORTEX
 THALAMUS
 HYPOTHALAMUS
 BRAINSTEM/ MIDBRAIN
 Periaqueductal gray (PAG)
 Nuclei raphe magnus
 Locus ceruleus
 Sub ceruleus
 SPINAL CORD
 SSC FLC

Cortex and
Thalamus
VPL MT

Hypothalamus
and Pituitary Sympathetic
PAG Outflow

Hypothalamic-
Pituitary Outflow
Midbrain
LC

Ascending Descending
Peripheral
Pathaways Pathaways
Nociceptor

Brainstem NRM
C-Fiber Sensory
Afferent

NSTT

PSTT Delta Sensory

Afferent

Spinal Cord
Sympathetic
Efferent

A-Alpha Motor
Efferent
MODULATION (noxious modulation)

 Refers to pain- suppressive mechanism within the

spinal cord dorsal horn neurons and at higher levels
of the brainstem and midbrain.
 In the spinal cord, this intrinsic “breaking
mechanism” inhibits oxious transmission at the
first synapse between the primary noxious afferent
and second order WDR and NS neurons.
 Thereby reducing spinothalamic relay of noxious
impulses.
 Spinal modulation is mediated by spinal-inter
neurons and terminal descending inhibitory.
SITES OF ENKEPHALIN BINDING IN SPINAL CORD.
ROLED BY INTRNEURON INHIBITORY AND DESCENDING FIBER INHIBITORY

Enkephalinergic
Interneuron
(Inhibitory)

Primary
Nociceptive
Presynaptic Opioid
Fiber
Receptors
(-)

ENK ENK

Postsynaptic
Opioid Glutamate
Receptors Receptors ENK
(-)
Descending
(+)
Enkephalinergic
Fiber (Inhibitory)

ENK

Spinal Sensory
Neuron
 Descending
Cortex
Modulatory Systems

PAG
Opioids

NRM LC

5-HT - - Enkephalin - Norepinephrine

Opioids Dorsal homs

 Descending Pain Control
Cortex
Brain Hypothalamus
Thalamus

Releases
• Endogenous opioids
Midbrain PAG • GABA
• NE

Releases
Brain stem NRM • Serotonin
• NE

Inhibit
Spinal cord DHN • WDR neurons Analgesia
• NS neurons
Thus, the role of DHN, is
the place where interaction
between afferent ascendern
input and descedern input.

1. MODULATION
2. TRANSMISSION
Modulation
 Pain

Medulation
Descending
modulation Dorsal Horn

Ascending Dorsal root

Conduction
input ganglion

Transduction
Spinothalamic Peripheral
tract nerve

Trauma
Peripheral
nociceptors

Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Perception
Pain Perception
Is the end result of the
Perception
neural activity starting
from Transduction, Pain
Brain
Conduction, Modulation Perception
and Transmission pain,
where pain becomes a
conscious
multidimensional
experience. Pain has
affective-motivational,
sensory-discriminative,
emotional and behavioral
components.
Pain has multidimensional
experience
1. sensory – discriminative
 Identifies the intensity, type and location of
pain
2. Affective – motivational
 Assessing the injury the meaning of injury

3. Emotional – behavioral component

 Attention, mood and behavioral due to pain.
 The Meaning of injury
Beecher

Prof. Hyodo
Sensitization theory by Woolf et
Is the net process starting from:
 Nociceptor activation
 Neural conduction
 Spinal transmission
 Noxious modulation
 Limbic & frontal – cortical perception
 Spinal & supra spinal response.
After the injury is occurred sensitization in
the periphery and centrally. (Hyperalgesia
and allodynia)
After tissue damage it occurs
peripheral and central
sensitization
Worst Pain

“Hyperalgesia” Normal
Response

No Pain
Allodynia

Increasing Stimulus Intensity

Stimulus response alteration observed with hyperalgesia

So, there are three
possibilities how do
we feel pain.
Noxious stimulus with Pain
Pain

Inhibition
CNS Modulation
Excitation

Nociception exp. normal situation

Nociception with Pain
Noxious stimulus without Pain
Pain
X Inhibition
CNS Modulation
Excitation

Example:
Nociception Stress Induced Analgesia

Nociception without pain

Pain without noxious stimulus
Pain

Inhibition
CNS Modulation
Excitation

X Example: Phantom Pain

Nociception Neurophatic Pain

Pain without nociception

SEKIAN
TERIMA KASIH BANYAK

SEMOGA ADA MANFAATNYA