Pain pathway........ which include some basic mechanisms of pain...

1. PRESENTED BY,
Dr. Sumit Rajewar
BDS, MDS
(Pedodontics and Preventive Dentistry)

2. CONTENTS
 Introduction
 Benefits of pain
sensations
 History
 Definition
 Characteristics of
pain
 Classification
 Components of pain
 Pain receptors
 Neural pain
pathways
 Sensory neurons
 Peripheral
mechanism of
injury induced pain
 Pain pathways
 Theories of pain

3.  Visceral pain
 Referred pain
 tooth pulp pain
Pain assessment visual analogue
scale
 Applied physiology
 Conclusion
 References

4. INTRODUCTION
 Pain is defined as unpleasant and emotional experience
associated with or without actual tissue damage.
 Pain sensation is describe in many ways like sharp,
pricking, electrical, dull ache, shooting, cutting, stabbing etc.
 As such, pain is typically associated with noxious stimuli,
events that are potentially or actually damaging to tissue.

5. Benefits of pain sensation
1) Pain gives us warning signal about the problems. It also
create awareness of injury.
2) Pain prevents further damage by causing reflex withdrawal of
the body from source of injury.
3) Pain urges the person to take proper treatment to prevent
major damage.

6. History
 Latin word ‘poena’ – punishment from God.
 Aristotle - first to distinguish 5 physical senses and considered pain
to be the ‘passion of the soul’
 Plato – contented pain and pleasure arose from within the body.
 The Bible – reference to pain not only in relationship to injury or
illness but also anguish of soul.

7.  Pain is, moreover, viewed either as a normal reaction to
an abnormal stimulus or as an abnormal response to a
normally harmless stimulus (Rasmussen, 1965).
 pain is a relative and subjective human experience, but it
may be accompanied by objectively discernible
phenomena, such as tachycardia, arterial hypertension,
hyperpnoea and vocalization, and a major purpose of
somatic pain seems to be, indirectly, that of inducing tissue
repair (Lim & Guzman, 1968)

8.  The pain threshold of the skin of a human subject, determined by electrical
stimulation, is almost the same throughout the body, but the face and neck
exhibit the relatively lowest values (Notermans, 1966).
 There is no appreciable difference between the threshold values of the right
and left side of the human body, nor any diurnal variation (Notermans, 1966).,
 Age and sex do not seem to influence the pain threshold (Hardy, Wolff &
Goodell, 1943), but the pain tolerance of females may be lower than that of
males, (Notermans & Tophoff, 1967).

10. An unpleasant sensory and emotional experience associated with actual or
potential tissue damage or described in terms of such damage.
- IASP
An unpleasant emotional experience usually initiated by a noxious stimulus
and transmitted over a specialized neural network to the central nervous
system where it is interpreted as such.
- Monheim
DEFINITION

11. CHARACTERSTICS OF PAIN
1. Threshold and Intensity
 If the intensity of the stimulus is below the threshold (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.)

12. 2. Adaptation – Pain receptors show no adaptation and so the pain
continues as long as receptors continue to be stimulated.
3. Localization of pain - Pain sensation is somewhat poorly
localized. However superficial pain is comparatively better
localized than deep pain.
4. 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.

13. CLASSIFICATION OF PAIN
Deep (from muscles/bones/fascia
/periosteum) e.g. fractures/arthritis
/fibrositis, rupture of muscle belly
PAIN
Somatic
(somasthetic
Visceral (from viscera)
e.g. angina pectoris, peptic
ulcer, intestinal colic, renal
colic, etc
Superficial (from skin &
subcutaneous tissue)
e.g. superficial
cuts/burns, etc

14. OROFACIAL PAIN CLASSIFICATIONOROFACIAL PAIN CLASSIFICATION
(OKESON)(OKESON)
AXIS I (physical conditions)
1. Somatic pain
A. Superficial Somatic pain
a. Cutaneous pain
b. Mucogingival
B. Deep Somatic Pain
a. Muscle pain
b. TMJ pain
c. Osseous pain
d. Periodontal pain
2. Visceral pain
a. Pulpal pain
b. Vascular pain
c. Neurovascular pain
d. Visceral mucosal pain
e. Glandular, ocular, auricular pain
AXIS II (psychologic conditions)
1. Mood disorders
2. Anxiety disorders
3. Somatoform disorders
4. Other conditions
 a. Psychologic factors affecting a
medical condition

15. Brain and spinal cord (CNS)

16. STRUCTURE OF A NEURON

18. STRUCTURE OF SPINAL CORD

20. Components of pain
FIBRE
TYPE
FUNCTION CONDUCTIO
N VELOCITY
(mts. / sec)
SPIKE
DURATIO
N
(milisec)
Myeli
nated
Fibre
s
Aα Proprioception, somatic
motor
30-120
0.4-0.5
Aβ Touch, pressure and motor
function
30-120
Aγ Motor to muscle spindles 15-35
Aδ Pain, temperature, touch 5-25
Myelinat
ed fibres
B Preganglionic autonomic
fibres
3-15 1.2
Unm
yelina
ted
Fibre
s
C
Pain, temperature, touch
and conducts impulses
generated by cutaneous
receptors
0.7-1.3 2

21. FAST PAIN
 Felt within 0.1 sec
 Sharp, pricking, acute,
electric pain
 When needle is struck into
the skin/electric shock/cuts
 Not felt in most deeper
tissues of body.
 Transmitted through A pain
fibres
SLOW PAIN
 Felt after a second or
more/maybe minutes.
 Burning, aching, throbbing,
chronic pain.
 Associated with tissue
destruction.
 Can occur in skin and in any
deep tissue or organ.
 Results from primitive type C
fibres.

22. SENSORY
COMPONENT MOTOR
COMPONENT

23. PAIN RECEPTORS
 Sensory Receptors :
 At the distal terminals are the afferent (sensory) nerves,
specialized sensory receptors that respond to physical or
chemical stimuli
 Once these receptors are adequately stimulated, an impulse is
generated in the primary afferent neuron that is carried centrally
into the CNS.
 Classified in 3 main groups:
1. Exteroreceptors
2. Proprioceptors
3. Interoreceptors

25. EXTEROCEPTORS
 Stimulated by immediate external environment.
 Provide information from the skin and mucosa.
 Examples:
1. Merkel’s corpuscles ( tactile receptors in the submucosa of
tongue)
2. Meissner’s corpuscles: tactile receptors in skin
3. Free nerve endings: perceive superficial pain and touch

26. PROPRIOCEPTORS
 Provide information from the musculoskeletal
structures concerning the position and movement of
the body.
 Automatic functioning
 Examples:
1. Muscle spindles: mechanoreceptors found
between skeletal muscle fibres.
2. Golgi tendon organs: mechanoreceptors in the
tendons of muscles signal muscle tension
3. Periodontal mechanoreceptors respond to
biomechanical stimuli

27.  Proprioception, which refers tooth position and movement of the limbs
(kinaesthesia), is determined by mechanoreceptors located in skin, joint
capsules and muscle spindles.
 The CNS integrates information received from these receptors, while
keeping track of previous motor responses that initiated limb movement
– a process known as efferent copy or corollary discharge (reviewed
by Matthews, 1982).

28. INTEROCEPTORS
 Located in and transmit impulses from viscera of the body.
 Examples:
1. Pacinian corpuscles: concerned with perception of pressure.
2. Free nerve endings: perceive visceral pain and other
sensations.

29. Development of Nociceptors
 Develop from neural crest stem cells.
 Neural crest cells are responsible mainly for development of the peripheral
nervous system.
 Cells split off from the neural tube as it closes, and nociceptors grow from
the dorsal part of this neural crest tissue.
 Forms late during neurogenesis.

30. Nociceptor
 Sensory input from various stimuli (either external or internal) is received
by specific peripheral receptors, called as nociceptors.
 Nociception – responds as transducers and transmit impulses.
 Perception of pain.
 Found in all areas of body.

31.  External nociceptors – skin, cornea and mucosa.
 Internal nociceptors – muscle, joint, bladder, gut and continuing along
the digestive tract.
 Cell bodies of these neurons are located in either the dorsal root
ganglia or the trigeminal ganglia.
 Trigeminal ganglia are specialized nerves for the face, whereas the
dorsal root ganglia associate with the rest of the body.

32. Sensory neurons
FIRST ORDER NEURONS
(POSTERIOR NERVE ROOT GANGLIA)
SECOND ORDER NEURONS
(SUBSTANTIA GELATINOSA
THIRD ORDER NEURONS
(THALAMIC NUCLEUS, RETICULAR FORMATION, TECTUM, GREY MATTER)
SOMATOSENSORY
CORTEX

33. 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.
It has long been known that a relationship exists between the diameter of
nerve fibers and their conduction velocities. The larger fibers conduct
impulses more rapidly than smaller fibers.
 A general classification of neurons divides the larger fibers from the smaller
ones.

34.  Type A fibers
 Alpha fibers: size - 13 to 20 µm, velocity - 70 to 120 m/ s.
 Beta fibers: size – 6 to 13 µm, velocity – 40 to 70 m/s.
 Gamma fibers: size – 3 to 8 µm, velocity – 15 to 40 m/s.
 Delta fibers: size – 1 to 5 µm, velocity – 5 to 15 m/s.
 Type C fibers
 Size – 0.5 to 1 µm, velocity – 0.5 to 2 m/s.

35. 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.

36. Third Order Neuron
 Cell bodies of third order neurons of the nociception-relaying pathway
are housed in: the ventro posterio lateral, the ventro posterioinferior, and
the intralaminar thalamic nuclei
 Third order neuron fibers from the thalamus relay thermal sensory
information to the somesthetic cortex.

37. Neurophysiology of Pain

38. Neurophysiology of Pain
TRANSDUCTION
TRANSMISSION
PERCEPTION
MODULATION

39. Transduction
 Activation of nociceptor.
1. Intense thermal and mechanical stimuli, noxious chemicals,
noxious cold
2. Stimulation of inflammatory mediators
 Damaged tissue release bradykinin, potassium, histamine,
serotonin and arachidonic acid.
 Arachidonic acid produce prostaglandins and leukotrienes.

40. Bradykinin + Leukotriene + Prostaglandin
Plasma extravasation
Edema
•PG stimulate nociceptors directly.

41.  LK stimulates nociceptors indirectly by PMNs
Release chemical mediators
Stimulates nociceptor
BK causes sympathetic nerve terminal to release PG thus stimulates
nociceptor.

42.  Sympathetic nerve terminal release another PG in
response to its own neurotransmitter (norepinephrine).
 Such ongoing inflammatory state causes physiologic
sensitization of nociceptors thus generating a response
even to a non-painful stimuli and exaggerated response
to noxious stimuli.

43. Transmission
 Process by which peripheral nociceptive information is
relayed to CNS.
 First order neuron synapses with the secondary order neuron
from where impulse is carried to higher structures of brain.
 Repeated or intense C fibre activation brings specific
changes on N-methyl-D-aspartate receptors resulting in
central sensitization, thus, response of second order neurons
increases as well as size of the receptive field also increases.

44. Perception
 It is the subjective experience of pain. It is the sum
of complex activities in CNS that may shape the
character and intensity of pain perceived and
ascribe meaning to pain.

45. Modulation
• It is the mechanism by which transmission of impulse to the brain is
reduced.
• Nociceptive transmission is influenced by :
a) Descending inhibitory systems that originate supraspinally
b) Periaqueductal gray
c) Nucleus raphe magnus
d) Nucleus tractus solitarius
e) Locus ceruleus/subceruleus
f) Endogenous opioid peptides

46.  Endogenous opioid peptides are naturally occurring pain-
dampening neurotransmitters and neuromodulators
employed in suppression and modulation of pain because
they are present in large quantities in areas of brain
associated with these activities.

47. Neurogenesis
NEW NEURONS GENERATED FROM NEURAL STEM CELLS AND
PROGENITOR CELLS.

48. Location of neurogenesis:
1) Subgranular Zone: (SGZ)
Found between the hilus and
granule cell layer and Dentate gyrus in
hippocampus.
Contains:
SGZ astrocytes
Precursor cells
Granule neurons
2) Subventricular Zone: (SVG)
Found along the wall of lateral ventricle as
layer of dividing cells.
Contains:
Neuroblast
SVZ astrocytes
Immature precursors

49. Process of Neurogenesis
(Cell proliferation)
 Cell proliferation is the generation of
new cells. These new cells are produced
within the ventricular zone.

50. Process of Neurogenesis
(Cell Migration)
 Cell migration is the
movement of newly
generated cells to their final
destination. Many daughter
cells (called neuroblasts)
migrate by slithering along
thin fibers (radial glial cells)
that radiate from the
ventricular zone toward the
pia

51. Process of Neurogenesis
(Cell Differentiation)
 This is the stage when a newly generated
cell begins to take on the appearance
and characteristics of a neuron.
Neuronal differentiation occurs first,
followed by astrocyte differentiation and
then oligodendrocyte differentiation.

52. 2nd
Part
(Pain pathway)
Contents:
Pain pathways
Theories of pain
Visceral pain
Referred pain
tooth pulp pain
Pain assessment visual
analogue scale
Applied physiology
Conclusion
References

53. PAIN IMPULSE PATHWAYPAIN IMPULSE PATHWAY

54. Fibers from lateral
spinothalamic tract
Fibers from lateral
spinothalamic tract
Ventral posterolateral nucleus of thalamus,
reticular formation & midbrain.
Ventral posterolateral nucleus of thalamus,
reticular formation & midbrain.
Sensory cortexSensory cortex
Receptor
First order neuron
Second order neuron
Third order neuron
center

55. Theories of pain:
1) Convergence Theory:
2) Facilitation Theory
3) Gate Control Theory

56. Convergence theory
 both somatic & visceral
afferent fibers converge upon
2nd
order neuron
Somatic fibers conduct
impulses more frequent.
Visceral pain is felt as
somatic pain because brain is
familiar with somatic regions.

57. Facilitation theory
Visceral & somatic fiber join at adjoining spinothalamic
neurons( 2nd
order neurons)
Activation of spinothalamic neurons occurs due to strong
impulses resulting in impulses passing through spinothalamic
pathway
This results in misinterpretation in location of pain.

58. Gate Control Theory
 Proposed by Ronald Melzack(Psychologist) & Pat-rick Wall
(Anatomoist)
 The pain stimuli transmitted by afferent fibers are blocked by
Gate mechanism located in posterior gray horn of spinal cord. If
gate is OPENED, pain is felt. If gate is CLOSED, pain is suppressed.

59. Mechanism of Gate Control at Spinal
cord:
 1) When pain stimulus is applied on any part of body, besides pain receptors,
then the receptor of other sensation such as touch sensation are also
stimulated.
 2) When all these impulses reach the spinal cord through posterior nerve root,
then the fibers of touch sensation sends collaterals to the neurons of pain
pathway
 3) Impulses of touch sensation to passing to these collaterals inhibit the
release of glutamate and substance-P from the pain fiber.
 4) This closes the gate and pain sensation gets blocked.

61. Significance of Gate Control:
 Due to this, relief of pain through rubbing, massage technique, application of
ice pack, acupuncture and electrical analgesia .

62. Visceral pain
They are dull & diffuse, poorly localized, and associated
with symptoms like nausea & referred to other areas
Stimuli for visceral pain
ischemia, obstruction, spasm, chemical stimuli.

63. Referred pain
Pain felt in a part of the body other
than its actual source
Pain at diaphragm is felt over tip of
shoulder
Pain at maxillary sinus felt at nearby
teeth.
A tooth abscess can cause jaw
bone pain.

64. Tooth pulp pain
1)Exposure of dentinal tubules
causes toothache & other non
noxious sensation.
2)Both Aδ & C fibers respond to
stimuli in dentine
3)Transmission of stimuli across
dentin, mediated by movement of
fluid in dentinal tubules.

65. 4) Fibers terminate at medullary dorsal horn & synapse and
also at trigeminal sensory nucleus
5) From trigeminal nucleus send to thalamus & sensory cortex
6) Pulpal innervation are capable of regenerating &
reinnervating

66. Determinants of painful experience during dental treatment
Pain occurs due to invasive procedures like extractions &
surgeries or non invasive procedures. With regard to children,
studies have shown that dentists do not believe in pain referred
by children & tend not to use available methods to control pain.
Conclusion: anxiety is determinant for pain during dental care &
pain is related to local anesthetic procedures. There are
evidences that dentists attitude are determinants for pain.

67. Pain assessment visual analogue scalePain assessment visual analogue scale

69. The sensory functions are affected by lesions in sensory
pathways or other nervous disorders.
1)Anesthesia – loss of sensation
2)Hyperesthesia- increase sensitivity to sensory stimuli
3)Hypoesthesia- decrease sensitivity to sensory stimuli
4)Hemiesthesia – loss of sensation to one part of body
5)Paresthesia- abnormal sensation

70. 6) Dissociated anesthesia- loss of some sensation with loss of
consciousness produced by anesthetic agents
7) General anesthesia- loss of all sensation with loss of
conciousness produced by anesthetic agents
8) Local anesthesia- loss of sensation restricted area of body
9) Tactile anesthesia- loss of tactile sensation

71. 10) Hyperaglasia-increase in sensitivity to pain
11) Paraglesia- abnormal pain sensation
12) Thermic anesthesia- loss of thermal sensation
13) Analgesia- loss of pain sensation

72. Herpes zoster:
Viral infection affecting dorsal root ganglion. Results in severe
pain which facilitates the pain towards the ganglion.

73. Symptoms:
 The earliest symptoms of herpes-Headache, Fever
1) Burning pain
2) Itching
3) Hyperesthesia
4) Paresthesia
 Pain can be mild to extreme in the affected dermatome, with sensations that
are often described as stinging, tingling, aching, numbing or throbbing.

74. Treatment:
 Analgesics
Mild to Moderate - Topical lotions containing calamine
Severe pain - Opioid medication such as morphine.
Once the lesions have crusted over, capsaicin cream can be used.
Topical lidocaine and nerve blocks may also reduce pain.
Administering gabapentin along with antivirals may offer relief of post
herpetic neuralgia

75. Antiviral:
Antiviral drugs may reduce the severity and duration but they do not prevent
post herpetic neuralgia.
Acyclovir has been the standard treatment, but the new drugs Valaciclovir and
Famciclovir having superior efficacy and good safety and tolerability.

76. Brown-Sequard syndrome
 All sensations are blocked at one side due to
Damage to one half of the spinal cord.
 Sensations like pain, heat & cold, vibrations are
Blocked.
Causes
1) Spinal cord tumour,
2) Trauma -such as a gunshot wound
3) Ischemia Due to obstruction of a blood vessel
3) Infectious
4) Inflammatory diseases such as tuberculosis

77. Trigeminal neuralgia:
Trigeminal neuralgia is a chronic pain disorder that affects the
trigeminal nerve.
Types:
1)Typical
2)Atypical

78. Treatment:
Medical t/t:
The anticonvulsant carbamazepine is the first line
treatment; second line medications include baclofen,
lamotrigine, oxcarbazepine, phenytoin, gabapentin and
pregabalin. Uncontrolled trials have suggested that clonazepam
and lidocaine may be effective.
Antidepressant medications, such as amitriptyline have
shown good efficacy in treating trigeminal neuralgia, especially if
combined with pregabalin.

79. Non destructive Surgery:
Microvascular decompression - this involves a small incision
behind the ear and some bone removal from the area. And
incision through the meninges to expose the nerve. Any
vascular compressions of the nerve are carefully moved
and a sponge-like pad is placed between the compression
and nerve.
Surgical t/t:

80.  Destructive Surgery:
•Glycerol injection- deposition of a corrosive liquid called
glycerol at this point causes damage to the nerve to hinder pain
signals.
•Radiofrequency (thermocoagulation rhizotomy) - application of
a heated needle to damage the nerve at this point.
•Stereotactic radiosurgery (gamma knife surgery)- is a form of
radiation therapy that focuses high-power energy on a small
area of the body

81. Conclusion
Pain can induce physiological & anatomical changes within the
nervous system. The complexity of pain transmission means
there are many pharmological targets & multimodel therapy is
required to optimize pain control.

82. THANK
YOU

83. References
Essential of oral physiology- Robert M Bradley
Textbook of medical physiology- Guyton & Hall
Essential of medical physiology- K.Sembulingam & Prema
Sembulingam
Textbook of human physiology- S Chand
Articles
•Determinants of painful experience during dental treatment-
Ruth Suzanne et al Rev.Dor 2012;13(4)
•Case report study on Brown sequard syndrome- Ponachi et al
Neurology Asia 2007;12;65-67
•Anatomy, physiology & pharmacology of pain- Ryan Moffat,
Colin P.Rae anesthesia & intensive care medicine; 2010;12(1)