Pain Perception

Theories of Pain Modulation

& Pain Gait Theory

By Dr. Shweta Desai

Assistant Professor
OBJECTIVES

 Introduction about Pain

 What is Nociception?
 Anatomy and Physiology of Pain Perception & Pain Pathway
 Theories of Pain Modulation
 Pain Gait Theory
INTRODUCTION
 Pain plays an important role in the survival of all animals.
 Purpose: alerting us to potential damage and leads to a range of
actions to prevent or limit further damage.

 Pain ‘system’ comprises a number of elements:

• Receptors Detect the noxious stimulus
• Convert it to a nerve impulse
• Transfer that impulse rapidly up the spine, the brainstem and
finally to the brain.
• Processed that stimulus
• Appropriate action is decided
Pain is a protective Mechanism, It occurs whenever any
tissue is damaged and it causes the individual to respond to
remove the Pain stimulus.
DEFINITION
 Pain is defined as an unpleasant sensory and emotional experience
that is associated with actual or potential tissue damage or described
in terms of such damage.
International association for the study of pain

 Pain is more than a physiological process and has emotional and

psychological aspects.

 Physiological process called Nociception

 Pain can be Experience in 2 Ways…

OBJECTIVE SUBJECTIVE

Actual Physiological Tissue Perceptual

Damage
Cognitive
Behavioral
What is nociception?

 The whole process of nociception can be

broken down in to four stages:

1. Transduction
2. Transmission
3. Perception
4. Modulation
1. Transduction

 Normal sensory receptors which respond to touch, pressure,

stretch, heat, cold etc.

 The body contains free nerve ending called nociceptors which

activate in response to noxious stimuli or pain.
 Pain receptors (Nociceptor)

Thermal Mechanical Chemical Polymodal

Triggered by Triggered by PH Changes or Triggered by
intense intense Result of more than 1
temperature Pressure Inflammation sensory
>45* c or <5* c (Pinch) modality

Aδ Fibers C Fibers
Any tissue injury causes the release
of inflammatory mediators like:

Bradykinins: Directly stimulate

nociceptors

Prostaglandin: Sensitization of the

nerve fibers

Histamine: Released by mast cells

to directly stimulate nociceptors

Serotonin (5-hydroxytryptamine):
Neurotransmitter
When cells are damaged, they release numerous chemical mediators
and cytokines

The activation of the nociceptor and an action potential is initiated

causing a nerve impulse

When these impulses are conducted centrally

The second step (transmission) is initiated

 2. Transmission
 Nerve impulse is transmitted from the
site of injury along the pain fiber
(neuron) to the dorsal horn of the
spinal cord

1st order neuron (Pain fiber)

 3 main types of nerve fibers:

• Aδ fiber
• Aβ fiber
• C fiber
 Aδ Fibers C Fibers Aβ Fiber
• Carry pain • Carry pain • Non-noxious stimuli
(Light Touch, Pressure,
Vibration)
• Impulses are carried by • Impulses are carried
small myelinated fibers by unmyelinated C • Highly myelinated and
at speeds around fibers at a speed of of large diameter
15m/sec about 1m/sec
• Fast conduction • Slow conduction • Fast Conduction
• Discrete sensitive spots • Found in all innervated
in the skin all over the body tissue
body surface and small
numbers in joints and
muscles
• Responsible for fast • Responsible for slow
pain pain
 Fast Pain Slow Pain
• It occurs within 0.1 second after the pain • It begins only after a second or more and
stimulus is applied then increase slowly over many seconds
and sometimes even minutes
• Occurs at the time of stimulation • Occurs when stimuli removed
• Sharp pain • Burning pain
• Prickling pain • Dull aching pain
• Acute pain • Throbbing pain
• Electric pain • Nervous pain
• Chronic pain
• Fast pain helps the body to avoid tissue • Associated with tissue destruction &
damage since it provokes an immediate sensitive to chemical released from the
reflex damaged tissues (Inflammatory changes)
• Well localized conscious awareness • Poorly localized
• Fast pain not felt in most deep tissue • Felt both in the superficial and deep
tissue
Within the spinal cord
 The 1st order pain fibers enter the dorsal horn of
the spinal cord and cross
 They activate 2nd order afferent pain fibers which
then carry the impulse up the contralateral
(opposite) side of the spinal cord to the brain.

 The nerve impulses are transmitted across the

synaptic cleft in the spinal cord to the 2nd order pain
fibers by neurotransmitters.

 The two important Neurotransmitters:

• Substance P: Neurotransmitter for C-fibers
• Glutamate: Neurotransmitter for Aδ fibers
Substance P: Neurotransmitter

The Role of Substance P:

• A neurotransmitter that is involved in the transmission of neuropathic and
inflammatory pain.
• To excite pain-transmitting neurons in the dorsal horn of the spinal cord
and to be involved in nociceptive processing at the spinal cord level.

Mode of action:
• Substance P may facilitate/excitation of afferent pain fibers by activating
the neurokinin-1 receptor in the spinal cord.
• When released into the periphery, Substance P increases the production of
inflammatory mediator prostaglandin and the release of cytokines from
macrophages and neutrophils.
 Located throughout the dorsal horn of the spinal cord

2 types of 2nd order neuron

Nociceptive Specific neuron Wide dynamic range neuron

(WDR)
Lamina I (Marginal Layer)
Lamina II (Substantia Gelatinosa) Lamina V

Receives inputs from Receives inputs from Receives inputs from

Nociceptors Aδ & C Nociceptors Aδ & C Non-Nociceptors Aβ
Fibers Fibers Fibers
Ascending tracts in the spinal cord

 The pain impulse is then transmitted up the

spinal cord to the brain via two main
ascending pathways.

The Spino-thalamic Tract The Spino-reticular Tract

• Carries mostly Aδ fibers • Carries mostly C fibers
• Through the • Through the reticular
Periaqueductal Gray formation in the Pons.
matter (PAG) in the
midbrain.
• Brainstem to Thalamus to • Brainstem to Thalamus to
Somatosensory cortex of limbic system.
the brain
• Plays a role in the
memory and emotional
components
 From the 1st order neuron

Neurotransmitters release

Glutamate, Substance P, Calcitonin gene-related peptide (CGRP)

Excites 2nd order neuron

Open Na+ and Ca+ Channels

Generation of Action Potential

Transmission of pain impulses through the Spinothalamic tract

Brainstem

Thalamus

The somatosensory cortex and other regions of the brain

3. Perception or Pain Processing in
the Brain )
 The perception of pain is the end result of pain transmission.

 The thalamus, which is the sorting center for the brain, receives
sensory impulses from various parts of the body.

 These signals are then passed to the relevant somatosensory cortex

area of the brain that processes the sensory information and the
perception of pain takes place.

 These signals are then passed to other locations of the brain.

3rd Order Neuron

From the thalamus (VPL Nucleus & Medial thalamic nuclei)

Hypothalamus Somatosensory Cortex

Limbic System
Stress Response Perception of Pain
Memory of Pain
Autonomic Emotional Response Discrimination &
Response Location of Pain
 The somatosensory cortex is
distorted such that the highly
sensitive areas of the body
take up a disproportionate
amount of space

• Ex: Because some areas of the

body (e.g. lips, hands) are
more sensitive to pain than
others, they require more
circuitry in the cortex to be
devoted to processing
sensations from them.
Nerve impulse travel in four
regions of the nervous system,
each of which can be modulated:

 Peripheral nervous system

(Receptors & Peripheral
Nerves)
 Spinal cord
 Brainstem and thalamus
 Cerebral cortex
4. Modulation or Inhibition of Pain
Transmission
 Nociceptive transmission throughout CNS is subject to modulation at
different numerous locations. (Peripheral level, Spinal level,
Supraspinal level, Cortical level)

 3 Theories :
A. Gait Control Theory / Pain Gait Theory / Ascending Inhibitory
Pathways
B. Supra spinal level modulation / Descending Inhibitory Pathways
C. Endogenous opioid system and pain inhibition
A. Gait Control Theory / Pain Gait Theory /
Ascending Inhibitory Pathways

 Inhibition of nociceptive transmission between 1st order Neuron and

2nd order neuron.

 Gait Control Theory / Pain Gait mechanism proposed by Melzack &

wall in 1965

 Proposes a mechanism for how pain is reduced

 By activating Non- Painful Stimuli (Non-nociceptive)

Large diameter non-nociceptive 1st order neuron (Aβ) afferent fibers

send input to the dorsal horn

Interfere with transmission of pain between nociceptor fibers and

dorsal horn neurons

By inhibiting gaiting activities in receptors (Gait Closing)

Deep touch activates the Pacinian corpuscle (Non- Noxious receptors)

Impulses carried by the Dorsal Column Medial Lemniscal Pathway

(DCML Pathway)

Activate inhibitory neuron

Release inhibitory neurotransmitters (Enkephalin, GABA)

Presynaptic Inhibition Postsynaptic Inhibition
Binds with opioid receptors situated on Binds with opioid receptors situated on
Aδ nerve fiber terminal 2nd-order neuron terminal

Closure of Na+ & Ca+ channels Opening of k+ channels

Less release of excitatory Decrease in Action Potential frequency

neurotransmitters

Decrease Pain signals sent to the brain

Less excitation of 2nd-order neuron

Decrease Action potential

Decrease Pain signals sent to the brain

 Hence that the reason when we are injured by some object we
have the tendency to rub that part which provides deep touch
sensation and pain gets reduced.

 This is known as synaptic inhibition at the spinal level

B. Supra spinal level modulation /
Descending Inhibitory Pathways

 By 3 ways of activation of descending analgesic pathway:

a) The spinothalamic tract and spino-reticular tract give
some extension into the midbrain and Pons
b) Limbic system
c) Somatosensory cortex

 Descending Modulation of pain transmission produced by

activation of many areas of the brain and brainstem.
• Midbrain: Periaqueductal
Grey Matter (PAG)

• Pons: Lateral Pontine

tegmentum – (Locus
Coeruleus)

• Medulla: Rostral ventral

medulla (RVM) – (Raphe
nucleus & Reticular Nuclei)
Descending inputs start from Periaqueductal Grey Matter (PAG) in the
midbrain (Rich in Serotonin- 5 HT)

From this inputs pass into the Locus Coeruleus in pons (Rich in
Noradrenaline and Norepinephrine)

From this region pass to various sub-regions of Rostral Ventral Medulla

(RVM) – (Raphe nucleus & Reticular Nuclei) (Rich in Serotonin- 5 HT)

Finally Descending pathway ends in to dorsal horn of the spinal cord

Norepinephrine and serotonin exert
their influence on 2nd order neuron

Excitatory effect on inhibitory

interneurons in the dorsal horn

Interneurons release opioids

(Enkephalin, GABA)
Presynaptic Inhibition Postsynaptic Inhibition
Binds with opioid receptors situated on Binds with opioid receptors situated on
Aδ nerve fiber terminal 2nd-order neuron terminal

Closure of Na+ & Ca+ channels Opening of k+ channels

Less release of excitatory Decrease in Action Potential frequency

neurotransmitters

Decrease Pain signals sent to the brain

Less excitation of 2nd-order neuron

Decrease Action potential

Decrease Pain signals sent to the brain

C. Endogenous opioid system and pain
inhibition
 During times of stress, pain, or emotion, the brain creates its own
analgesia through the secretion of endogenous opioids from multiple
points in the central nervous system (CNS).

1. Periaqueductal Grey Matter (PAG)

2. Rostral ventral medulla (RVM)
3. Locus Coeruleus (LC)
4. Hypothalamus
5. Dorsal horn of spinal cord


 Endogenous Substance:
• Β endorphin
• Methionine
• Enkephalin
• Endomorphin
• Dynorphin

 Produce analgesia
 Both Presynaptic and Post synaptic
Evidence

P Labour patients

I TENS

C Routine obstetric care

O VAS
Transcutaneous electrical nerve
stimulation (TENS) reduces pain and
postpones the need for
pharmacological analgesia during
labour: a randomised trial
 JOURNAL & LEVEL OF AIMS METHODOLOGY CONCLUSION
AUTHORS EVIDENCE
• Journal of • 1 RCT • To assess the effect • The principal • TENS produces
PHYSIOTHERA of Transcutaneous investigator a significant
PY electrical nerve applied TENS to decrease in pain
• Santana et al stimulation (TENS) the experimental during labour
on pain reduction group for 30 and postpones
and postpones the minutes starting the need for
need for at the beginning pharmacological
pharmacological of the active analgesia for
analgesia during phase of labour. pain relief.
labour. Participants in
both groups
received all other
routine obstetric
care.
References

 Electrotherapy Explained: Principles & Practice: John Law and Ann Read
 Clayton’s Electrotherapy
 Clinical electrophysiology: Robinson
 Electrotherapy: Basanta Kumar Nanda