Physiology of Pain

Department of Physiology
Sailesh Chaudhary
 Learning Objectives
• Introduction to pain
• Types of pain receptors
• Classification of pain
– Fast pain
– Slow pain
• Pain Pathways
• Modulation of pain
– Gate control Theory
– Gate control theory revisited
– Endogenous pain relief system
• Referred pain
– Projected pain
– Phantom pain
 Introduction
• Pain is a sensory experience of special significance to
physicians & protective reflex
• causes the individual to react to remove the painful stimulus
and prevent the movement of damaged part initiation of
withdrawal response & avoidance response
• Intensely subjective experience, and is therefore difficult to
describe
• Two features-
– Unpleasant experience
– Evoked by a stimulus which is potentially damaging to living
tissues
• Pain has two component
– Awareness of a painful stimuli
– Emotional impact evoked by the experience
 Introduction contd…

• Pain is defined by the (IASP) as, “an unpleasant

sensory and emotional experience associated with
actual or potential tissue damage”
• Nociception- as the unconscious activity induced by a
harmful stimulus applied to sense receptors
 Pain receptors
• Free nerve endings & respond to wide variety of stimuli
(Polymodal)
• All the stimuli to which pain receptors respond potentially
damaging or noxious ( Nociceptors)
• Adapt poorly to a prolonged stimulus & allows the pain to
keep the person apprised of a tissue-damaging stimulus as
long as it persists
• Types of Nociceptors
– Mechanical Nociceptors (Strong pressure)
– Thermal Nociceptors (above 45 °C or by severe cold
below 10 )
– Chemical Nociceptors (bradykinin, histamine etc)
– Polymodal Nociceptors (combination of all stimuli)
 Found
• Maximally in the skin (fast pain receptors are present only
on skin)
• A significant n.o - periosteum, arterial walls, joint surfaces
• Deep viscera are poorly supplied by pain receptors
• No pain receptors at all in the brain

Note: Organ which perceives pain cannot itself detect any

painful stimulus
Causes of Pain: noxious stimuli
 Physiological classification of pain
A. Fast pain (felt within about 0.1)
– conducted by thinly myelinated fibres A delta (2–5 μm in
diameter which conduct at rates of 12–30 m/s, well localized &
sharp or pricking in character & Not felt in most deeper tissues
– Sharp pain, pricking pain, acute pain & electric pain
B. Slow pain (begins only after 1 second or more)
– conducted by unmyelinated C fibres (0.4–1.2 μm in diameter)
which conduct at low rates of 0.5–2 m/s, poorly localized &
burning or dull and aching in character
– Slow burning pain, aching pain, throbbing pain, nauseous pain &
chronic pain
– occur both in the skin and deep tissue or organ
– Associated with tissue destruction & can lead to prolonged
almost unbearable suffering
Fast pain: can be elicited by mechanical & thermal stimuli

Slow pain: can be elicited by all three types of stimuli

Transmission of both pain signals into and through the
spinal cord on their way to the brain
 Pain path ways

Cross section of the spinal cord

 Pain pathways
• Fast pain (Glutamate)
– An important role in making the
person react immediately to remove
himself or herself from the stimulus
bcz rapidly damaging
– Central axons of these neurons
terminate mainly in lamina I & also
in laminae II & V of the dorsal horn
of the spinal cord
– Synapse with projection neurons
which continue as the
neospinothalamic tract on the
contralateral side & give off
collaterals in the RF, tectum & PAG
– Relay in the ventrobasal complex
(topographic) which provides the 1st
station where all types of stimuli from
a given part of the body relay
 Pain pathways contd..
• project to the sensory cortex in a
topographic manner & organized in
modality specific columns
• Columns dedicated to pain are far
fewer than touch & that is why pain itself
is not as accurately localized as touch
• Slow pain (Substance P)
– conveyed to the dorsal horn of the
spinal cord mainly in lamina II
(substantia gelatinosa)
– Projection neurons for slow pain
travel in the paleospinothalamic tract
& Give off much more collaterals
– Relay in the nonspecific nuclei &
poorly localized, and has a greater
potential for keeping us awake
 Transmission of pain signals into the brain stem,
thalamus, and cerebral cortex

Note: pain impulses entering the brain stem reticular formation, the
thalamus, and other lower brain centers cause conscious perception of
pain
cortex plays an especially important role in interpreting pain quality
 Modulation of pain

• Noxious stimuli of comparable intensity may produce varying

degrees of pain in the same individual under different

circumstances

• Pain can be modulated & for modulation of pain was

proposed in the 1960s by Ronald Melzack and Patrick Wall in

the form of gate control theory

 Gate control theory

• Modulation of pain at the spinal cord level by the simultaneous

presence of non-noxious stimuli
• Touch stimulus is applied to the same area of skin which has been
subjected to a noxious stimulus
• Touch fiber gave a collateral in the substantia gelatinosa of the
which, in turn inhibited the pain fiber presynaptically through an
inhibitory interneuron
• Touch stimulus could reduce the painfulness of a noxious stimulus

• Inhibitory interneuron acts as a gate & when it is activated the

gate is closed and pain impulses cannot ascend upwards
Gate control theory contd…..
• Presence of other
competing stimuli
reduces the ferocity of
pain
• E.g- generating a
strong sensation over a
painful joint by
application of a cream
reduces the pain
• Pains are felt more
acutely at night when
competing stimuli are
absent than during the
day
 Endogenous pain relief system
• Body has an in-inbuilt system for reducing the intensity of
pain
• A capability of the brain itself to suppress input of pain signals
to the nervous system by activating a pain control system-
analgesia system
• Stimulation of several areas of the CNS produces a specific
analgesic response
• Important areas is the PAG
• Receptors for morphine & opioid receptors are present in
all the major relay stations concerned with pain (substantia
gelatinosa, RF, PAG & intralaminar thalamic nuclei as well as
throughout limbic system)
• Endorphins & serotonin found as neurotransmitters in CNS
where opioid receptors are present
 Endogenous pain relief system contd..
• Descending fibres which parallel
the ascending fibres converge in
the PAG & activation of PAG
neurons which releases serotonin
in the substantia gelatinosa
• Serotonin in turn, activates
enkephalinergic interneurons
which inhibit the projection
neurons of the pain pathway &
modulate the intensity of pain
• Any form of stress activates the
analgesic system through the
limbic system
• Inhibition of incoming pain signals
at spinal cord by descending
fibers
 Gate control theory revisited

• Inhibitory interneurons are not activated by touch &

primary afferents
• Instead inhibitory interneurons seem to activated by
descending from PAG & related areas
• Dorsal column fibres, while ascending to the thalamus, give off
collaterals to the RF which activate the descending fibres of
the endogenous analgesic system
• Touch stimulus can still close the gate, although indirectly
Revaluation of the gate control theory
 Referred pain

• Irritation of a visceral organ frequently produces pain that is

felt not at that site but in some somatic structure that may be
a considerable distance away
• E.g- inflammation of the appendix produces pain around the
umbilicus & GB often produces pain at the right shoulder
• The common point between the site of the referred pain & the
diseased organ is that both are innervated by the same
segment of the spinal cord
 Referred pain contd..

• When pain is referred, it is structure that developed from the

same embryonic segment or dermatome as the structure in
which the pain originates
• Since the brain often receive information about painful stimuli
only from the superficial parts of the body, it interprets an
occasional painful stimulus from a deep organ also as
originating superficially
Two types of neuronal circuitry responsible for the
phenomenon of referred pain

convergence of somatic & visceral pain fibers on the same 2nd order
neurons that project to the thalamus & then to the somatosensory
cortex- covergence projection theory
 Projected pain
• If pain fibers are stimulated mechanically or electrically on their
way to the spinal cord, the brain still interprets the pain as
originating in the part of the body where the corresponding
nociceptors are located
• E.g- if the pain fibres travelling in the ulnar nerve are stimulated
at the elbow, the pain is still perceived to originate in the hand
 Phantom pain

• Amputation of a limb, the cut ends of severed nerves

innervate the skin covering the stump (part of limb)
• Stimuli existing the nerve fibres at the stump are interpreted
as originating in the limb which does not exist any more
• The phantom limb sometimes also experiences pain, which
is known as phantom pain
• Bcz the brain has been interpreting signals conveyed by
those nerve fibres as coming from the lost limb
 Summary
• What is pain? (Definition of pain)
• Types of pain
• Pain receptors (nociceptors)
• Pain stimuli (noxious stimuli)
• Causes of Pain
• Afferent nerves that carry pain impulse
• Pain path ways:
-Neospinothalamic pathway for fast pain
-Paleospinothalamic pathway for slow pain
• Modulation of Pain:
-Gate control theory
-Revisited gate control theory
-Endogenous pain relief system
• Visceral pain
• Referred pain: Mechanism of referred pain
• Phantom pain
THANK
YOU
“Ishrat-e-katra hai dariya mein fana ho jana. Dard ka had
se guzarna hai dawa ho jana”