Physiology of Pain Pathways and Its Modulation: DR Hassan
Physiology of Pain Pathways and Its Modulation: DR Hassan
Physiology of Pain Pathways and Its Modulation: DR Hassan
DR HASSAN
What is Pain???
• The International Association for
the Study of Pain (IASP) defines
pain as "an unpleasant sensory
and emotional experience
associated with actual or
potential tissue damage, or
described in terms of such
damage."
• Derived from Latin -“Poena” meaning
Penalty/punishment from God.
• JCAHO declared pain as fifth vital sign (1999).
• Net effect of a complex interaction of the
ascending and descending nervous systems
involving biochemical, physiologic,
psychological and neocortical processes.
Classification Of Pain:-
Duration Acute
Chronic
Acute on chronic
Cause Cancer
Non cancer
Mechanism Nociceptive (physiological)
Neuropathic (pathological)
• Pain that is caused by noxious stimulation
due to injury, a disease process, or the
abnormal function of muscle or viscera.
• Two types of acute (nociceptive) pain
somatic and visceral.
CLASSIFICATION OF ACUTE PAIN
ACUTE PAIN
Finally leading to
NEUROPATHIC PAIN
NOCICEPTIVE VS NEUROPATHIC PAIN
NOCICEPTIVE PAIN NEUROPATHIC PAIN
Well localized Not well localized
Burning
Sharp Shooting
Worse with movement Numbness
Pins and needles
Obvious tissue injury or Tissue injury may not be
illness obvious
Nerve injury
Changes in wiring
Inflammation
Abnormal firing
Loss modulation
Physiological pain * Pathological pain
REFERRED PAIN
• Pain that is perceived at the site different from
its point of origin but innervated by the same
spinal segment.
•Convergence Theory:
21
VISCERAL NOCICEPTORS:-
• visceral nociceptors include those in internal organs.
• Visceral organs are generally insensitive tissues that
mostly contain silent nociceptors.
• Most organs such as the intestine are innervated by
polymodal nociceptors that respond to smooth muscle
spasm, ischemia and inflammation.
• These receptors generally don’t respond to cutting
,burning or crushing that occurs during surgery.
•Noxious sensations can often be broken down
into two components(DOUBLE PAIN):-
•A fast (sharp) and a slow (burning) sensation.
• The fast phase is mediated by myelinated
fibers (A).
• The slow and delayed pain is mediated by
unmyelinated fibers (C-fibers).
• This distinction has been used to explain the
phenomenon of double-pain.
• Afferent activity from these neurons enters the
spinal cord between T1 and L2.
• Fibers from the esophagus, larynx, and trachea
travel with the vagus nerve to enter the nucleus
solitarius in the brain stem.
• Fibers from the bladder, prostate, rectum,
cervix and urethra, and genitalia are
transmitted into the spinal cord via
parasympathetic nerves at the level of the S2–
S4 nerve roots.
• FAST PAIN • SLOW PAIN
• Felt about 0.1 sec after a pain • Usually begins after 1 sec or
stimulus is applied. more and may range from
• Serotonin
• Endorphins
Pain • Enkephalins
Inhibitors • Dynorphin
• GABA
• Glycine
THREE NEURONS
DUAL
ASCENDING PATHWAY
First Order Neuron:-
• Pseudounipolar cell (dorsal root ganglion) ,
divides into central and peripheral branch.
• Impulses are transmitted by Aδ fibre or C fibres.
• Cell bodies located in dorsal root ganglia.
• These impulses are transmitted through the
axons to spinal cord.
• axons of first order neurons may synapse with
interneurons, sympathetic neurons and ventral
motor neurons.
SECOND ORDER NEURONS
• Second order neurons consist of -
• Nociceptor specific primarily in LAMINA I
• Wide Dynamic Range(WDR) neurons
primarily in LAMINA V
• Nociceptive specific neurons serve only noxious
stimuli, but WDR neurons also receive non
noxious afferent input from Aβ, A∂ and C fibers.
• Cell body in the Spinal Cord or medulla
oblongata.
• Spinal cord grey matter was divided by
REXED into ten lamina.
• The first six lamina, which make up the
dorsal horn, receive all afferent neural
activity, and represent the principal site of
modulation of pain by ascending and
descending neural pathways.
• Lamina II also called the SUBSTANSIA
GELATINOSA ,contains many interneurons
It is believed to be a major site of action for
opioids.
• Lamina V contains WDR neurons ,responds
to both noxious and non noxious sensory
input and receives both visceral and somatic
pain afferents. Thus responsible for referred
pain.
• THIRD ORDER NEURON:-
• located in the thalamus and send
fibers to somatosensory areas 1
and 2 in the postcentral gyrus of
the parietal cortex and the
superior wall of the sylvian
fissure respectively.
-Modulation;-Perception
•MODULATION OF PAIN
• Modulation of pain occurs
• - peripherally at the nociceptors ,
- spinal cord
-supraspinal structure.
• This modulation can either inhibits or facilitates
pain.
• The major site of modulation is dorsal horn of
spinal cord.
PERIPHERAL MODULATION
• Nociceptors and their neurons display
sensitization following repeated stimulation.
• It occurs by two mechanisms:
• PRIMARY HYPERALGESIA (exaggerated
response to pain at site of injury)
SECONDARY HYPERALGESIA (response to
pain outside the site of injury)
PRIMARY HYPERALGESIA
• Sensitization of nociceptors commonly occurs
with injury and following application of heat.
• Primary hyperalgesia is mediated by the
releaseof alogens from damaged tissues:-
1) Bradykinin- macrophages
2) Histamine- platelets and mast cells
3) Serotonin
4) Prostaglandin
Peripheral Sensitization
Reduced Transduction Threshold
Primary hyperalgesia
Primary heat allodynia
Innocuous/Noxious
stimulus
Inflammation
They sensitize or
activate receptors.
Neurons release
substance P, which
stimulates mast cells
and blood vessels.
Histamine released
from mast cells and
bradykinin released
from blood vessels add
to pain stimulus.
What are the Modulators
Of peripheral Sensitisation?
Central Sensitization
• Substance P
• Vasoactive Intestinal Peptide (VIP)
• Cholecystokinin (CCK)
• Angiotensin
• L-glutamate
• L-aspartate
•Mechanism Of Action:-
•These substances trigger changes in
membrane excitability by interacting with G
protein–coupled membrane receptors on
neurons, activating intracellular second
messengers, which in turn phosphorylate
substrate proteins.
•A common pathway is an increase in
intracellular calcium concentration.
• Glutamate and aspartate receptors play an
important role in wind up via activation of
NMDA and non NMDA receptor mechanism.
Figure 10-12a
The Gate-Control Theory of Pain
Figure 10-12b
The Gate-Control Theory of Pain
ACUPUNCTURE
AND TENS
Figure 10-12c
• The introduction of the gate control theory in
1965 [Melzack &Wall 1965] has acted as a
catalyst for the global proliferation of the
different techniques for pain alleviation based
on afferent stimulation, such as
transcutaneous electric nerve stimulation
[TENS] and ACUPUNTURE.
Mechanisms Of Action Of TENS
• Afferent activity set up by TENS inhibits
nociceptive transmission in the spinal cord
through pre as well as post synaptic inhibitory
mechanisms. Not only the spinal cord but also
the thalamic regions may be involved.
THANK YOU