PHYSIOLOGY OF PAIN

Vaibhav Jain
 Contents

Introduction

Historical Perspective

Classification of Pain

Pain Pathways

Pain Perception

Pain Modulation

Conclusion
 What is Pain?
Pain is a vital function of the nervous system in providing the body with
a warning of potential or actual injury.
It is both a sensory and emotional experience, affected by psychological
factors such as past experiences, beliefs about pain, fear or anxiety.
The International Association for the Study of Pain formulated
definition states: Pain is an unpleasant sensory and emotional
experience associated with actual or potential tissue damage, or
described in terms of such damage.
 Historical Views of Pain

Prior to the the scientific renaissance in Europe pain was not well-
understood, and it was thought that pain originated outside the body,
perhaps as a punishment from God.
Hippocrates believed that it was due to an imbalance in vital fluids.

In 1644, Ren Descartes theorized that pain was a disturbance that

passed down along nerve fibers until the disturbance reached the brain.
In 1965, Ronald Melzack along with Patrick David Wall proposed the
gate control theory of pain.
 Descartes' Pain Pathway

Particles of heat (A) activate a spot of skin

(B) attached by a fine thread (C) to a valve in
the brain where this activity opens the valve,
allowing the animal spirits to flow from a
cavity (F) into the muscles causing them to
flinch from the stimulus, turn the head and
eyes toward the affected body part, and move
Source: Traite de l'homme;1664
the hand and turn the body protectively.
 Classifying Pain

Pain has been classified into two major types:

Fast Pain is felt within about 0.1 second after a pain stimulus is applied,
described by many alternative names, such as sharp pain, pricking
pain,, electric pain or acute pain.
Slow Pain begins only after 1 second or more and then increases slowly
over many seconds and sometimes even minutes, also described as
aching pain, throbbing pain, nauseous pain or chronic pain.
 Pain Receptors

Pain is termed nociceptive and activate nociceptors which are free nerve
endings found in the skin muscle, joints, bone and viscera.
Recently, it was found that nerve endings contain transient receptor
potential (TRP) channels that sense and detect damage.
They transduce a variety of noxious stimuli into receptor potentials, which
in turn initiate action potential in the pain nerve fibers.
The cell bodies of nociceptors are mainly in the dorsal root and trigeminal
ganglia. No nociceptors are found inside the CNS.
 Types of Nociceptors

Skin Nociceptors, mechanonociceptors, thermal nociceptors,

chemical nociceptors, and polymodal nociceptors.
Joint Nociceptors, mechanoreceptors and polymodal nociceptors.
Visceral Nociceptors, mechanonociceptors, thermal nociceptors, and
chemical nociceptors.
Sleeping/Silent Nociceptors, become awakened to mechanical
stimulation only on the onset of inflammation.
 Activatation of Nociceptors

Factors that activate nociceptors includes:

Globulin and protein kinases

Histamine
Nerve growth factor (NGF)

Substance P

Calcitonin gene-related peptide (CGRP) Fig. | Activation of the nociceptors

Potassium (K+) ion

Muscle spasm and lactic acid

 Sources of Pain

Somatic pain: Pain that arises from the skin, muscles, joints or peripheral
nerves themselves.
Visceral Pain: In the visceral organs, nociceptors respond to mechanical
stimulation such as pressure, tissue damage, and chemical stimulation.
Neuropathic Pain: Pain caused by damage or disease affecting the
somatosensory nervous system may be associated with dysesthesia or
allodynia.
 Referred Pain: Referred pain is a painful sensation at a site other than
the injured one.
Psychogenic Pain: Physical pain that is caused, increased, or prolonged
by mental, emotional, or behavioral factors.
Incident Pain: Incident pain is pain that arises as a result of activity,
such as movement of an arthritic joint, stretching a wound, etc.
 Phantom Limb Pain

Fig. | Areas involved in the Fig. | Mirror box therapy

generation of phantom limb pain
Cancer Pain

Fig. | Mechanism of Cancer Pain

 Nociceptive Pathway
Fig. | Peripheral ganglia

Somatosensory neurons are located in

peripheral ganglia located alongside the
spinal column and medulla.

Afferent neurons project centrally to the

brainstem and dorsal horn of the spinal
cord and peripherally to the skin and other
organs.
 Nociceptive Fibres

Most nociceptors are unmyelinated with

small diameter axons (C-fibers, red),
projects to superficial laminae I and II of
the dorsal horn.

A-fiber nociceptors are myelinated with

conduction velocities (A-fibers, blue),
Fig. | Pain Tracts
projects to superficial laminae I and V.
Ascending Pain Pathways
 Perception of Pain

The perception of pain is complex and subjective, and is affected

by factors such as cognition, mood, beliefs and external enviroment.
The somatosensory cortex is important for the localisation of pain.

However, imaging techniques such as fMRI have demonstrated that

a large brain network is activated during the acute pain experience.
Thalamus, reticular formation and limbic system are important
centres for pain perception. This is often called the pain matrix.
Neuroimaging of Pain

I. Tracey Br. J. Anaesth. 2008;101:32-39

Factors Influencing Pain Perception
Pain Modulation

Fig. | Gate Control Theory of Pain

 Pain Sensitization

Noxious stimuli can sensitize the

nervous system response to
subsequent stimuli.
The normal pain response as a
function of stimulus intensity is
depicted by the curve at the right.
However, a traumatic injury can Fig. | Pain Sensitization

shift the curve to the left.

 Analgesia System
Fig. | Descending pain pathway

The capability of the brain itself to suppress

input of pain signals to the nervous system by
activating a pain control system, called an
analgesia system.
Electrical stimulation either in the
periaqueductal gray area or in the raphe
magnus nucleus can suppress many strong
pain signals entering by way of the dorsal
spinal roots.
Opiates Analgesia

SM Parsadaniantz et. al, 16, 6978 (2015)

 Stress-Induced Analgesia

Exposure to a variety of painful or stressful events produces an

analgesic reaction. This phenomenon is called stress induced
analgesia (SIA).
SIA has been thought to provide insight into the psychological
and physiological factors that activate endogenous pain control
and opiate systems.
For example, soldiers wounded in battle or athletes injured in
sports events.
 Congenital Analgesia

In humans, SCN9A gene encodes

the -subunit of the voltage-gated
sodium Na+ channel (Nav1.7),
which is strongly expressed in
nociceptive neurons.
Mutation in SCN9A gene causes
congenital inability to experience
Fig. | Nav1.7 voltage gated channel
pain.
 Pain Management

Physical approach
Physical medicine and rehabilitation
Acupuncture

Psychological approach
Mindfulness Meditation
Hypnosis
Cognitive behavioral therapy (CBT)
Interventional approach
Neurolytic Block
Deep brain stimulation (DBS)
Pharmacologic Approach
 Conclusion

Pain is both a sensory and emotional experience, and patients past

experiences, fears and anxieties can play an important role.
Pain perception is a result of the balance between facilitatory and
inhibitory interactions modulated at different levels.
Current areas of interest in pain research include investigating the effect
of mood on pain processing in the brain and looking for novel drugs to
block channels involved in pain transmission.
 References

Guyton and Hall, Textbook of Medical Physiology, 13th Edition.

Eric R. Kandel, Principles of Neural Science, 5th edition.

Dale Purves, Neuroscience, 5th edition.

Imaging Pain; I. Tracey Br. J. Anaesth. 2008; 101:32-39.

Flor et al. Nature Reviews Neuroscience. 2006; 873881.

Parsadaniantz et al. Nature Reviews Neuroscience. 2015; 6978.

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