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Pain and its pathways
Abhishek Roy
II Year PG
OMFS
Contents
• Introduction
• Definition
• Incidence of pain
• Characteristics of pain
• Theories of pain
• Neurochemistry of pain
• Types of pain
• Pain receptors
• Pain pathway
• Inhibition of pain
• Conclusion
• References
Introduction
• Pain is a sensory experience of special
significance to physicians and basic
scientists.
• It is one of the most common symptoms
which physicians are called to treat.
• The study of physiology of pain has taught
us about various pathways of neural
function.
Definition of Pain
• The International Association for the Study of
Pain defined it as an unpleasant sensory and
emotional experience associated with actual
or potential tissue damage, or described in
terms of such damage.
Incidence of pain
• A study was conducted by Sukhvinder et al
which concluded that toothache (57.6 %) was
the most commonly reported symptom and
burning mouth sensation (6.4 %) was the least
commonly reported. Majority of the patients had
grade 3 level of pain-related disability (34.8 %)
followed by grade 2 (26.8 %), grade 1 (22.4 %)
and grade 4 levels (16 %).
Prevalence of Various Orofacial Pain Symptoms and Their Overall Impact on Quality of Life in a
Tertiary Care Hospital in India
Sukhvinder Singh Oberoi, S. S. Hiremath, R. Yashoda, Charumohan Marya, Amit Rekhi
J Maxillofac Oral Surg. 2014 Dec; 13(4): 533–538. Published online 2013 Sep 14. doi:
10.1007/s12663-013-0576-6
Characteristics of Pain
• Threshold and Intensity :
• If the intensity of the stimulus is below the threshold
level (sub-threshold), pain is not felt
• As the intensity increases more and more, pain is
felt more and more according to the Weber-
Fechner’s law. This law ensures that while our body
can perceive pain due to low intensity stimulus, a
severe crushing injury will not cause death due to
pain sensation, yet as stimulus increases, sense of
perception also increases.
Characteristics of Pain (contd.)
• Adaptation – Pain receptors show no adaptation
and so the pain continues as long as receptors
continue to be stimulated.
• Localization of pain - Superficial pain is
comparatively better localized than deep pain.
• Influence of the rate of damage on intensity of
pain. If the rate of tissue injury (extent of damage
per unit time) is high, intensity of pain is also
high.
Factors influencing pain perception
• Emotional status
• Fatigue
• Age
• Fear and apprehension
• Previous experience of pain
Theories of Pain
Intensity theory
• Stated by Goldscheider
based on experiments by
Naunyn in 1859
• Pain is produced when any
sensory nerve is stimulated
by a non-specific sensation
and depends on the
application of high intensity
stimulation
• Disproved for examples like
trigeminal neuralgia where
a gentle touch in a pressure
zone provides excruciating
pain.
Specificity Theory
• Postulated by Johannes Muller
in 1842
• Pain is a specific modality
equivalent to vision and
hearing
• It is mediated by free nerve
endings just as Meissner
corpuscles for touch and
Ruffini end organs for warmth
• No longer tenable as free
nerve endings are almost
absent from hairy skin and
cannot be specific receptors to
warmth and cold
Pattern Theory
• Goldscheider,1894
• Pain sensation depends
upon spatio-temporal
pattern of nerve impulses
reaching brain
• Warmth, cold and pain
describe reproducable
codes of neural activity
evoked from skin by
changes in environment
Gate Control Theory
• Proposed by Melzack and Wall in 1965
• This theory of pain takes into account the relative
input of neural impulses along large and small
fibers
• The small nerve fibers reach the dorsal horn of
spinal cord and relay impulses to further cells
which transmit them to higher levels
• The large nerve fibers have collateral branches,
which carry impulses to substantia gelatinosa
where they stimulate secondary neurons
Gate Control Theory (contd.)
• The substantia gelatinosa cells terminate
on the smaller nerve fibers just as the
latter are about to synapse, thus reducing
activity, the result is, ongoing activity is
reduced or stopped – gate is closed
• The theory also proposes that large
diameter fiber input has ability to modulate
synaptic transmission of small diameter
fibers within the dorsal horn
Neurochemistry of Pain
Neurochemistry of Pain
 Damage to tissue cells produces
leakage of intracellular contents
including potassium and histamine,
both of which either activate or
sensitize the nociceptor
• Other compounds such as
acetylcholine, serotonin, and ATP
maybe released by tissue damage and
are known to either activate or
sensitize nociceptors
• Another group of compounds that
synthesize the regions of tissue
damage are the metabolic products of
arachidonic acid. These compounds
are considered inflammatory
mediators and include both
prostaglandins and leukotrienes
• Bradykinin is one of the most potent
pain producing substances that
appears in injured tissue. Bradykinin is
a powerful vasodilator and causes
increased capillary permeability
Neurochemistry of Pain
Pain Receptors
• Sensory Receptors -
• Sensory input from various external stimuli is thought to be
received by specific peripheral receptors that act as
transducers and transmit by nerve action potentials along
specific nerve pathways toward the central nervous system.
• Termed first–order afferents, these peripheral terminals of
afferent nerve fibers differ in the form of energy to which they
respond at their respective lowest stimulus intensity, that is,
are differentially sensitive.
• The impulse interpreted is nociceptive (causing pain) if it
exceeds the pain threshold, that is, the intensity of the stimulus
is so great that the receptor is no longer differentially sensitive.
Nociceptors
• A nerve ending that responds to noxious stimuli that can
actually or potentially produce tissue damage.
• Free nerve endings - The receptors for fast pain are
sensitive to mechanical or thermal stimuli of noxious
strength.
• The receptors for slow pain are sensitive not only to
noxious mechanical and thermal stimuli but also to a wide
variety of chemicals associated with inflammation :
histamine, serotonin, bradykinin, acetylcholine, potassium
ions and hydrogen ions.
Types of Nociceptors
•Aδ Mechanical Nociceptors
•C Polymodal Nociceptors
•C fibre mechanical nociceptors
•High threshold cold nociceptors
First Order Neuron
• Each sensory receptor is attached to a first
order primary afferent neuron that carries
the impulses to the CNS
• The axons of these first-order neurons are
found to have varying thickness
• The larger fibers conduct impulses more
rapidly than smaller fibers
Second Order Neuron
• The primary afferent neuron carries impulse
into the CNS and synapses with the second-
order neuron
• This second-order neuron is sometimes
called a transmission neuron since it transfers
the impulse on to the higher centers
• The synapse of the primary afferent and the
second-order neuron occurs in the dorsal
horn of the spinal cord
Third Order Neuron
• Cell bodies of third order neurons of the
nociception-relaying pathway are housed in -
» the ventral posterior lateral nuclei
» the ventral posterior inferior nuclei
» the intralaminar thalamic nuclei
 Third order neuron fibers from the thalamus
relay thermal sensory information to the
somatosensory cortex
Pain Pathways
Spinothalamic tract
Spinothalamic tract
• It is a sensory pathway from the skin to
thalamus
• Sensory information is relayed upward from
the ventral posterolateral nucleus in the
thalamus, to the somatosensory cortex of the
postcentral gyrus.
• The pathway decussates at the level of the
spinal cord, rather than in the brainstem like
the dorsal column-medial lemniscus pathway
and lateral corticospinal tract
Spinothalamic tract (contd.)
• The spinothalamic tract consists of two
adjacent pathways
– anterior
– lateral
• The anterior spinothalamic tract carries
information about crude touch
• The lateral spinothalamic tract conveys
pain and temperature
Lateral Spinothalamic tract
Lateral Spinothalamic tract
• It is also called the lateral spinothalamic
fasciculus
• It carries pain and temperature sensory
information (protopathic sensation) to the
thalamus
• It is composed primarily of fast-conducting,
sparsely myelinated A delta fibers and
slow-conducting, unmyelinated C fibers
Lateral Spinothalamic tract
• From the site of pain
generation(from the periphery)
the pain senses are carried by
Aδ & C fibres
• Their cell bodies are situated
in the dorsal root ganglion.
• The central processes of the
neuron, lying in the ‘sensory
root’ of the spinal nerve enter
the dorsal horn to terminate in
the SGR ( Substantia
gelatinosa Rolandi), situated in
the tip of dorsal horn
Lateral Spinothalamic tract
• From the SGR, 2nd order
neuron arises,
decussates and then
moves up through the
white matter of spinal
cord to reach the brain
• These secondary
neurons are situated in
the posterior horn,
specifically in the Rexed
laminae regions I,II, IV, V
and VI
Lateral Spinothalamic tract
• The Rexed laminae comprise
a system of ten layers of grey
matter (I-X), identified in the
early 1950s by Bror Rexed to
label portions of the grey
columns of the spinal cord
• Specific importance in pain
pathway are -
– Region II - Substantia
Gelatinosa of Rolando which
carries out modulation of pain
– Region VI - Base of dorsal
horn through which “fast pain”
travels and flexion reflex is
controlled
Lateral Spinothalamic tract
• These fibers will ascend through
the brainstem, including the
medulla oblongata, pons and
midbrain, as the spinal
lemniscus until synapsing in the
ventroposteriorlateral (VPL)
nucleus of the thalamus
• The third order neurons in the
thalamus will then project
through the internal capsule and
corona radiata to various
regions of the cortex, primarily
the main somatosensory cortex,
Brodmann areas 3, 1, and 2.
Lateral Spinothalamic tract
• At SGR, there is a synapse between 1st
order & 2nd order neuron. Also there is
synapse of 2nd & 3rd order neuron at
thalamus
• The neurotransmitter at the synapse
between Aδ fiber & 2nd order neuron at
SGR is glutamate while the NT between C
fiber & 2nd order neuron (slow pain) at
SGR is substance P
Primary somatosensory cortex
• The primary somatosensory
cortex is located in the
postcentral gyrus, and is part
of the somatosensory system
• Conventionally, areas 3,1,2
have been regarded as the
primary somatosensory cortex
• Recent studies by Kaas has
shown that only area 3 should
be referred to as "primary
somatosensory cortex", as it
receives the bulk of the
thalamocortical projections
from the sensory input fields
Dual Pain Pathways in Cord &
Brainstem
Neospinothalamic Tract for Fast Pain
• The fast type A(δ) pain fibers transmit
mainly mechanical and acute thermal pain
• They terminate mainly in lamina I at the
dorsal horn and these excite second order
neurons of the neospinothalamic tract
Paleospinothalamic tract for Slow
Pain
• This pathway transmits pain mainly from
peripheral slow chronic Type C pain fibers
• In this pathway, the peripheral fibers
terminate almost entirely in lamina II and III
of dorsal horns of spinal cord, together
called as substantia gelatinosa
Inhibition of pain
• Pain sensations may be controlled by interrupting
the pain impulse between receptor and
interpretation centers of brain
• This may be done chemically, surgically or by
other means
• Most pain sensations respond to pain reducing
drugs/analgesics which in general act to inhibit
nerve impulse conduction at synapses
• Occasionally however, pain may be controlled
only by surgery.
Drugs for dental pain
 NSAIDS -
–Ibuprofen
–Naproxen
–Aspirin
Surgical Approaches
• Sympathectomy – excision of portion of
neural tissue from autonomic nervous
system
• Cordotomy – severing of spinal cord tract,
usually the lateral spinothalamic
• Rhizotomy – cutting of sensory nerve roots
• Prefrontal lobotomy – destruction of tracts
that connect the thalamus with prefrontal
and frontal lobes of cerebral cortex
Transcutaneous Electrical
Nerve Stimulation (TENS)
• With TENS, cutaneous bipolar surface electrodes are
placed in the painful body regions and low voltage
electric currents are passed
• Best results have been obtained when intense stimulation
is maintained for at least an hour daily for more than 3
weeks
• TNS portable units are in wider spread use in pain clinics
throughout the world and has been proved most effective
against neuropathic pain
Transcutaneous Electrical
Nerve Stimulation (TENS)
• TENS is a method of electrical stimulation
which primarily aims to provide a degree of
symptomatic pain relief by exciting sensory
nerves and thereby stimulating either the
pain gate mechanism and/or the opioid
system
Conclusion
• Pain is a multidimensional experience involving
both the sensation evolved by noxious stimuli but
also the relation to it
• The sensation of pain therefore depends in part
on the patient past experience, personality and
level of anxiety
• The most important part of managing pain is
understanding the problem and cause of pain.
• It is only through proper diagnosis that
appropriate therapy can be selected
References
• Bell`s ‘Orofacial pain’, 5th edition, Jeffrey P. Okeson
• Text book of Medical Physiology, 2nd edition, Chaudhari
• Text book of Medical Physiology, 10th edition, Arther C
Gyton
• Text book of ‘Oral medicine’- 10th edition, Burkett’s
• Gray's Anatomy – 38th Edition, Churchill Eivingstone
• Online sources
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Pain and its pathways

  • 1.
  • 2. Pain and its pathways Abhishek Roy II Year PG OMFS
  • 3. Contents • Introduction • Definition • Incidence of pain • Characteristics of pain • Theories of pain • Neurochemistry of pain • Types of pain • Pain receptors • Pain pathway • Inhibition of pain • Conclusion • References
  • 4. Introduction • Pain is a sensory experience of special significance to physicians and basic scientists. • It is one of the most common symptoms which physicians are called to treat. • The study of physiology of pain has taught us about various pathways of neural function.
  • 5. Definition of Pain • The International Association for the Study of Pain defined it as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
  • 6. Incidence of pain • A study was conducted by Sukhvinder et al which concluded that toothache (57.6 %) was the most commonly reported symptom and burning mouth sensation (6.4 %) was the least commonly reported. Majority of the patients had grade 3 level of pain-related disability (34.8 %) followed by grade 2 (26.8 %), grade 1 (22.4 %) and grade 4 levels (16 %). Prevalence of Various Orofacial Pain Symptoms and Their Overall Impact on Quality of Life in a Tertiary Care Hospital in India Sukhvinder Singh Oberoi, S. S. Hiremath, R. Yashoda, Charumohan Marya, Amit Rekhi J Maxillofac Oral Surg. 2014 Dec; 13(4): 533–538. Published online 2013 Sep 14. doi: 10.1007/s12663-013-0576-6
  • 7. Characteristics of Pain • Threshold and Intensity : • If the intensity of the stimulus is below the threshold level (sub-threshold), pain is not felt • As the intensity increases more and more, pain is felt more and more according to the Weber- Fechner’s law. This law ensures that while our body can perceive pain due to low intensity stimulus, a severe crushing injury will not cause death due to pain sensation, yet as stimulus increases, sense of perception also increases.
  • 8. Characteristics of Pain (contd.) • Adaptation – Pain receptors show no adaptation and so the pain continues as long as receptors continue to be stimulated. • Localization of pain - Superficial pain is comparatively better localized than deep pain. • Influence of the rate of damage on intensity of pain. If the rate of tissue injury (extent of damage per unit time) is high, intensity of pain is also high.
  • 9. Factors influencing pain perception • Emotional status • Fatigue • Age • Fear and apprehension • Previous experience of pain
  • 11. Intensity theory • Stated by Goldscheider based on experiments by Naunyn in 1859 • Pain is produced when any sensory nerve is stimulated by a non-specific sensation and depends on the application of high intensity stimulation • Disproved for examples like trigeminal neuralgia where a gentle touch in a pressure zone provides excruciating pain.
  • 12. Specificity Theory • Postulated by Johannes Muller in 1842 • Pain is a specific modality equivalent to vision and hearing • It is mediated by free nerve endings just as Meissner corpuscles for touch and Ruffini end organs for warmth • No longer tenable as free nerve endings are almost absent from hairy skin and cannot be specific receptors to warmth and cold
  • 13. Pattern Theory • Goldscheider,1894 • Pain sensation depends upon spatio-temporal pattern of nerve impulses reaching brain • Warmth, cold and pain describe reproducable codes of neural activity evoked from skin by changes in environment
  • 14. Gate Control Theory • Proposed by Melzack and Wall in 1965 • This theory of pain takes into account the relative input of neural impulses along large and small fibers • The small nerve fibers reach the dorsal horn of spinal cord and relay impulses to further cells which transmit them to higher levels • The large nerve fibers have collateral branches, which carry impulses to substantia gelatinosa where they stimulate secondary neurons
  • 15. Gate Control Theory (contd.) • The substantia gelatinosa cells terminate on the smaller nerve fibers just as the latter are about to synapse, thus reducing activity, the result is, ongoing activity is reduced or stopped – gate is closed • The theory also proposes that large diameter fiber input has ability to modulate synaptic transmission of small diameter fibers within the dorsal horn
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  • 18. Neurochemistry of Pain  Damage to tissue cells produces leakage of intracellular contents including potassium and histamine, both of which either activate or sensitize the nociceptor • Other compounds such as acetylcholine, serotonin, and ATP maybe released by tissue damage and are known to either activate or sensitize nociceptors • Another group of compounds that synthesize the regions of tissue damage are the metabolic products of arachidonic acid. These compounds are considered inflammatory mediators and include both prostaglandins and leukotrienes • Bradykinin is one of the most potent pain producing substances that appears in injured tissue. Bradykinin is a powerful vasodilator and causes increased capillary permeability
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  • 21. Pain Receptors • Sensory Receptors - • Sensory input from various external stimuli is thought to be received by specific peripheral receptors that act as transducers and transmit by nerve action potentials along specific nerve pathways toward the central nervous system. • Termed first–order afferents, these peripheral terminals of afferent nerve fibers differ in the form of energy to which they respond at their respective lowest stimulus intensity, that is, are differentially sensitive. • The impulse interpreted is nociceptive (causing pain) if it exceeds the pain threshold, that is, the intensity of the stimulus is so great that the receptor is no longer differentially sensitive.
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  • 23. Nociceptors • A nerve ending that responds to noxious stimuli that can actually or potentially produce tissue damage. • Free nerve endings - The receptors for fast pain are sensitive to mechanical or thermal stimuli of noxious strength. • The receptors for slow pain are sensitive not only to noxious mechanical and thermal stimuli but also to a wide variety of chemicals associated with inflammation : histamine, serotonin, bradykinin, acetylcholine, potassium ions and hydrogen ions.
  • 24. Types of Nociceptors •Aδ Mechanical Nociceptors •C Polymodal Nociceptors •C fibre mechanical nociceptors •High threshold cold nociceptors
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  • 28. First Order Neuron • Each sensory receptor is attached to a first order primary afferent neuron that carries the impulses to the CNS • The axons of these first-order neurons are found to have varying thickness • The larger fibers conduct impulses more rapidly than smaller fibers
  • 29. Second Order Neuron • The primary afferent neuron carries impulse into the CNS and synapses with the second- order neuron • This second-order neuron is sometimes called a transmission neuron since it transfers the impulse on to the higher centers • The synapse of the primary afferent and the second-order neuron occurs in the dorsal horn of the spinal cord
  • 30. Third Order Neuron • Cell bodies of third order neurons of the nociception-relaying pathway are housed in - » the ventral posterior lateral nuclei » the ventral posterior inferior nuclei » the intralaminar thalamic nuclei  Third order neuron fibers from the thalamus relay thermal sensory information to the somatosensory cortex
  • 33. Spinothalamic tract • It is a sensory pathway from the skin to thalamus • Sensory information is relayed upward from the ventral posterolateral nucleus in the thalamus, to the somatosensory cortex of the postcentral gyrus. • The pathway decussates at the level of the spinal cord, rather than in the brainstem like the dorsal column-medial lemniscus pathway and lateral corticospinal tract
  • 34. Spinothalamic tract (contd.) • The spinothalamic tract consists of two adjacent pathways – anterior – lateral • The anterior spinothalamic tract carries information about crude touch • The lateral spinothalamic tract conveys pain and temperature
  • 36. Lateral Spinothalamic tract • It is also called the lateral spinothalamic fasciculus • It carries pain and temperature sensory information (protopathic sensation) to the thalamus • It is composed primarily of fast-conducting, sparsely myelinated A delta fibers and slow-conducting, unmyelinated C fibers
  • 37. Lateral Spinothalamic tract • From the site of pain generation(from the periphery) the pain senses are carried by Aδ & C fibres • Their cell bodies are situated in the dorsal root ganglion. • The central processes of the neuron, lying in the ‘sensory root’ of the spinal nerve enter the dorsal horn to terminate in the SGR ( Substantia gelatinosa Rolandi), situated in the tip of dorsal horn
  • 38. Lateral Spinothalamic tract • From the SGR, 2nd order neuron arises, decussates and then moves up through the white matter of spinal cord to reach the brain • These secondary neurons are situated in the posterior horn, specifically in the Rexed laminae regions I,II, IV, V and VI
  • 39. Lateral Spinothalamic tract • The Rexed laminae comprise a system of ten layers of grey matter (I-X), identified in the early 1950s by Bror Rexed to label portions of the grey columns of the spinal cord • Specific importance in pain pathway are - – Region II - Substantia Gelatinosa of Rolando which carries out modulation of pain – Region VI - Base of dorsal horn through which “fast pain” travels and flexion reflex is controlled
  • 40. Lateral Spinothalamic tract • These fibers will ascend through the brainstem, including the medulla oblongata, pons and midbrain, as the spinal lemniscus until synapsing in the ventroposteriorlateral (VPL) nucleus of the thalamus • The third order neurons in the thalamus will then project through the internal capsule and corona radiata to various regions of the cortex, primarily the main somatosensory cortex, Brodmann areas 3, 1, and 2.
  • 41. Lateral Spinothalamic tract • At SGR, there is a synapse between 1st order & 2nd order neuron. Also there is synapse of 2nd & 3rd order neuron at thalamus • The neurotransmitter at the synapse between Aδ fiber & 2nd order neuron at SGR is glutamate while the NT between C fiber & 2nd order neuron (slow pain) at SGR is substance P
  • 42. Primary somatosensory cortex • The primary somatosensory cortex is located in the postcentral gyrus, and is part of the somatosensory system • Conventionally, areas 3,1,2 have been regarded as the primary somatosensory cortex • Recent studies by Kaas has shown that only area 3 should be referred to as "primary somatosensory cortex", as it receives the bulk of the thalamocortical projections from the sensory input fields
  • 43. Dual Pain Pathways in Cord & Brainstem
  • 44. Neospinothalamic Tract for Fast Pain • The fast type A(δ) pain fibers transmit mainly mechanical and acute thermal pain • They terminate mainly in lamina I at the dorsal horn and these excite second order neurons of the neospinothalamic tract
  • 45. Paleospinothalamic tract for Slow Pain • This pathway transmits pain mainly from peripheral slow chronic Type C pain fibers • In this pathway, the peripheral fibers terminate almost entirely in lamina II and III of dorsal horns of spinal cord, together called as substantia gelatinosa
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  • 47. Inhibition of pain • Pain sensations may be controlled by interrupting the pain impulse between receptor and interpretation centers of brain • This may be done chemically, surgically or by other means • Most pain sensations respond to pain reducing drugs/analgesics which in general act to inhibit nerve impulse conduction at synapses • Occasionally however, pain may be controlled only by surgery.
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  • 49. Drugs for dental pain  NSAIDS - –Ibuprofen –Naproxen –Aspirin
  • 50. Surgical Approaches • Sympathectomy – excision of portion of neural tissue from autonomic nervous system • Cordotomy – severing of spinal cord tract, usually the lateral spinothalamic • Rhizotomy – cutting of sensory nerve roots • Prefrontal lobotomy – destruction of tracts that connect the thalamus with prefrontal and frontal lobes of cerebral cortex
  • 51. Transcutaneous Electrical Nerve Stimulation (TENS) • With TENS, cutaneous bipolar surface electrodes are placed in the painful body regions and low voltage electric currents are passed • Best results have been obtained when intense stimulation is maintained for at least an hour daily for more than 3 weeks • TNS portable units are in wider spread use in pain clinics throughout the world and has been proved most effective against neuropathic pain
  • 52. Transcutaneous Electrical Nerve Stimulation (TENS) • TENS is a method of electrical stimulation which primarily aims to provide a degree of symptomatic pain relief by exciting sensory nerves and thereby stimulating either the pain gate mechanism and/or the opioid system
  • 53. Conclusion • Pain is a multidimensional experience involving both the sensation evolved by noxious stimuli but also the relation to it • The sensation of pain therefore depends in part on the patient past experience, personality and level of anxiety • The most important part of managing pain is understanding the problem and cause of pain. • It is only through proper diagnosis that appropriate therapy can be selected
  • 54. References • Bell`s ‘Orofacial pain’, 5th edition, Jeffrey P. Okeson • Text book of Medical Physiology, 2nd edition, Chaudhari • Text book of Medical Physiology, 10th edition, Arther C Gyton • Text book of ‘Oral medicine’- 10th edition, Burkett’s • Gray's Anatomy – 38th Edition, Churchill Eivingstone • Online sources