Pathways of pain

1. Dr Gauri Kapila
MDS 2nd year
Department of Periodontology
and Oral Implantology
PAIN PATHWAYS

2.  Introduction
 Functional neuroanatomy & pathways
 Neurophysiology of pain
 Neurochemistry of nociception
 Theories of pain
 Pain modulation
 Types of pain
 Pain evaluation and measurement
 Dual nature of pain
 Factors affecting pain reaction
 Conclusion

3.  Latin word “poena” : “punishment, penalty, hardship,
suffering”
 Greek word “poine” : “punishment"
 An unpleasant sensation associated with actual or
potential tissue damage and mediated by specific nerve
fibres to the brain, where its conscious appreciation may
be modified by various factors
* Stedman’s Medical Dictionary, ed 27. Baltimore: Lippincott Williams
and Wilkins, 2000: 1297

4. WHO
• International association for the study of pain (IASP)
• An unpleasant emotional experience associated with
actual or potential tissue damage or described in terms
of such damage.
Bell
• The subject’s conscious perception of modulated
nociceptive impulses that generate an unpleasant
sensory and emotional experiences associated with
actual or potential tissue damage or describe in terms
of such damage.
Monheims
• An unpleasant emotional experience usually initiated by
noxious stimulus and transmitted over a specialized
neural network to CNS where it is interpreted as such.

5. Fields : Subjective experience to pain arises by 4
distinct processes
Transduction
Noxious
stimuli
Electrical
activity
Transmission
Neural events
that carry the
nociceptive
input into the
CNS
Modulation
Ability of the
CNS to
control the
pain-
transmitting
neurons
Perception
Subjective
experience of
pain

7.  Distal terminals afferent nerves are specialized sensory receptors
 Called sensor-transducers or receptors
 Classified in 3 main groups
 Exteroceptors
 Proprioceptors
 Interoceptors

8. Exteroreceptor Function
Merkel’s corpuscles Tactile receptors (in submucosa of
tongue and oral mucosa)
Meissner’s corpuscles Tactile receptors in the skin
Ruffini’s corpuscles Pressure & warmth.
Krause’s corpuscles Cold receptors
Free nerve endings Superficial pain & touch
Meissner’s
corpuscles

9. Proprioceptor Function
Muscle spindles Mechanoreceptors.Myotactic
reflex
Golgi tendon bodies Mechanoreceptors,role in
nociception
Pacinian corpuscles Perception of pressure
Free nerve endings Deep somatic pain
& other sensations
Periodontal mechanoreceptors Biomechanical stimuli
 Provide information from the musculoskeletal structures concerning the
presence, position & the movement of the body
Automatic functioning

10.  Periodontal ligament : Abundantly supplied by sensory nerve
fibers
 Free nerve endings
 Ruffini’s corpuscles : Apical area
 Meissner’s corpuscles : Midroot region
 Encapsulated spindle : Apex

11.  Interoceptors
 Inside the body
 Transmit impulses from the viscera of the body
Interoreceptors Function
Pacinian corpuscles Perception of pressure
Free nerve endings Visceral pain & other sensations

12.  Responsible for identifying tissue injury
 Free nerve ending : Non encapsulated branching of the axon
 Receptive field: tissue area for which nociceptors responsible
 Polymodal: performing more than one type of functions
C-fiber mechano/heat-sensitive
nociceptors(CMH)-burning type
A-fiber mechano/heat-sensitive
nociceptors(AMH)-pricking type

13.  Afferent neuron that carries the impulses from sensory receptor to CNS
Type of fiber Size ( In µm) Velocity (In
m/sec)
A α 13 - 20 70 -120
A β 6 - 13 40 -70
Aγ 3 –8 15 -40
Aδ 1 - 5 5 - 15
C 0.5 -1 0.5 - 2

14. 14Pain Pathways

15.  Second order neurons
 Transmission neurons : Transfer impulse to the higher centres
 Ascend in the form of lateral spinothalamic tract

16.  3 different types of second order neurons
Low threshold
mechanosensitive
neurons (LTMN)
• Light touch,
pressure &
proprioception
Nociceptive
specific neurons
(NSN)
• Noxious stimulation
Wide dynamic
range neurons
(WDRN)
• Wide range of
stimulus intensities
from non-noxious to
noxious stimuli

17.  Dorsal horn of the spinal cord : Laminae
 I to VI
 Nociceptive input : Laminae I,II and V

18.  In the dorsal horn- Interneurons present : Transmit impulses to other
interneurons/Ascending neurons
 Significant population of these interneurons in the laminae II and III
Inhibitory
Excitatory

19. Light touch and proprioception
Leminiscal systemAnt/Lat. STT
Pain,crude touch,temperature

20. Paleospinothalamic
tract
Neospinothalamic
tract

21.  Neospinothalamic tract
 Lamina I
 A-delta fibres directly to the thalamus. Carries fast pain.
 Carries mechanical and thermal pain
 Paleospinothalamic tract
 Lamina II and III and V
 The NS neurons project various interneurons through reticular
formation -enter thalamus
 The nociceptive impulse can thus be modulate/changed
 Thus takes longer to reach-lower pain conduction

22.  Third order neurons
 Neurons of thalamic nucleus, reticular formation, tectum & gray
matter around Aqueduct of Sylvius
 Axons from these neurons reach the sensory area of cerebral
cortex
 Simultaneously sent to the hypothalamus and limbic structure
 Centre for pain sensation: Post central gyrus of parietal cortex

23.  Nerve conduction
 Function of nerve : Carry messages from one part of the body to
another
 Action potential : Impulses
Action potential is a transient membrane depolarization that result from
brief increase in permeability of the membrane to sodium and due to
delayed increase in permeability to potassium

24.  Resting State
 Resting potential : -70mV
 Slightly permeable to Na+ ions
 Freely permeable to K+ ions
 Freely permeable to Cl- ions

25. Resting potential
-70mV
Slow
depolarization
Threshold / firing
potential
Rapid
depolarization
Reversal of
polarity
+40mV
Repolarization
Depolarization : 0.3 msec
Repolarization : 0.7 msec
Entire process : 1 msec

27.  Synapse
 Interneuronal junctions
 Presynaptic terminals : Small knobs
(on the surface of dendrites)
 Synaptic cleft : 200 to 300Å in size

28.  Presynaptic terminals
 Synaptic vesicles-Excitatory/inhibitory
 Mitochondria
(has ATP -synthesize new transmitter substances)

29. Receptor protein and Ionophore component

30.  Ion Channels
 Pre-synaptic membrane
 Voltage-gated ion channels:Sodium ion channel, potassium
channel, calcium channel
 G-protein-linked ion channels: Bradykinin, 5HT (5-
hydroxytryptamine) and prostaglandins.
 Ligand-gated ion channels:5-HT, acetylcholine glutamate, GABA

31. Rapid-acting
neurotransmitters
Excitatory agents
Acetyl choline,
Norepinephrine, Glutamate,
Aspartate, Histamine, Nitric
Oxide
Inhibitory agents
Serotonin, Gamma Amino
Butyric Acid (GABA),Glycine,
Dopamine
Slow-acting
neurotransmitters
(Neuropeptides)
Excitatory agents
Substance P, Bradykinin
Inhibitory agents
Endorphins

32.  Elimination of the transmitter from the synapse
 Diffusion
 Enzymatic destruction
 Re-uptake

34.  Sources of various chemical compounds are:
 Damaged cell
 Secondary effects of plasma extravasation
 Secondary effects of lymphocyte migration
 Nociceptor

35. Damage to tissue cells : Leakage of intracellular contents
Potassium and histamine : Activate or sensitise the nociceptors
Arachidonic acid : PGs activated.
Substance P produced antidromically : activates mast cells ,blood vessel, platelets
Histamine,Bradykinin,Serotonin thus released respectively
This influences the release of another primary afferent neuron- Primary Hyperalgesia

36.  Specificity theory
 Descartes (1644) : Pain system as a straight-through channel from the
skin to the brain
 Muller (19th century) : Information transmission only by way of the
sensory nerves
 Von Frey (late 19th century) : Specific cutaneous receptors for the
mediation of touch, heat, cold and pain

37.  Free nerve endings : Pain receptors
 Pain “centre”: Exist within the brain, responsible for all over
manifestation of the unpleasant experience
 Surgical procedures for management of chronic pain—by straight
cutting through tracts
 Does not explain the inhibition or exaggeration of pain by emotion or
the continued presence of pain after surgical removal of a body part
with its receptors

38.  Intensity theory
 Pain produced when any sensory nerve is stimulated beyond a
certain level
 This theory states that if electric current stimulates teeth;
threshold sensation is variously described as hot, cold, tingling,
etc, but if intensity increases it gives sensation as pain
 But the trigeminal theory is an example against the theory. In this
case patient with trigeminal neuralgia exhibits pain from the
stimulus no greater than general touch

39.  Pattern theory
 Goldscheider (1894) : Stimulus intensity & central summation are
the critical determinants of pain
 Particular patterns of nerve impulses that evoke pain are produced
by the summation of sensory input within the dorsal horn of spinal
column
 Pain results when the total output of the cells exceeds a critical
level
eg: Touch + Heat + Pressure = Pain

40.  Protopathic and Epicritic Theory
 Postulated by Head and Rivers, 1908
 Protopathic group carries diffuse impressions of pain
 The epicritic group was sensitive to touch discriminations and
small changes in temperature
 This theory was the stepping stone to gate control theory

41.  Gate control theory
 Melzack & Wall (1965)
 Large diameter ("touch, pressure, vibration") and thin ("pain")
fibers meet at 2 places in the dorsal horn of the spinal cord
 Transmission (T) cells
 Inhibitory (I) cells
Dr. Ronald Melzack Dr. Patrick Wall

42. Large fiber +Thin fiber excite the T cells
Inhibitory cells : Inhibit activation of the T cells
T cells : Gate on pain
T
T
T
Large fiber : Excite Inhibitory cells

43.  Gate control theory
 Neural impulses : Modulated as they ascend to higher centre
 Facilitation : Impulses Accentuate pain experience
 Inhibition : Impulses Lessen pain experience
 Melzack and Wall assume that peripheral non-noxious stimulation
will inhibit presynaptically the pain conducting impulses at the
spinal cord target cells (T cells) and will prevent pain sensation
from being transmitted to higher centers

44.  Pain modulation : Various levels of the CNS
 Trigeminal spinal tract nucleus
 Reticular formation
 Descending inhibitory system
 Psychologic modulating factors

45.  Trigeminal Spinal Tract Nucleus
 Trigeminal spinal tract nucleus : Brainstem extension of the spinal
dorsal horn
 T cell : 2nd order neuron
 I cell : Inhibitory interneurons in
substantia gelatinosa

47.  Transcutaneous Electrical Nerve Stimulation
 Rationale : Anti-nociceptive effect of
stimulating cutaneous sensory nerves
 Interrupted faradic current of very low intensity at a frequency of
50 to 100 Hz
 Stimulation less than that required to activate A-delta and C fibers
 Antinociceptive effect : Stimulation of thick A-beta fibers

48.  Reticular Formation
 Certain areas of the reticular formation have concentrated cells
(nuclei) that produce certain neurotransmitters which can be:
 Excitatory : Enhance the ascending neural input
 Inhibitory : Block the ascending input
 Quickly released & destroyed : Fast acting
 Slowly released & remain in the synapse for long periods : Long
lasting

49.  Descending Inhibitory System

50.  Affect all sensory input
ascending into brainstem
Analgesic system (3 parts):
 Periaqueductal(PAG)
 Nuclues Raphes Magnus(NRM)
 Descending neurons
 Affects nociceptive input

51.  Endorphins
 Inherent endogenous anti-nociceptive system : modulates pain
 Inhibited by Naloxone
 Acute pain : Endogenous opioids into CSF& bloodstream
 Enkephalin : Very short, lasts only a few seconds
 Bloodstream beta-endorphin : Delayed and lasts for longer periods

52.  Acupuncture and Electroacupuncture
 Needle Acupuncture/Electric current
 Noxious stimulation of acupoints
 Release of beta-endorphin into the peripheral circulation
 Current of sufficient intensity to cause pain & phasic muscle
contractions, at a very low frequency (2 Hz)

53. Excitatory modulating factors Inhibitory modulating factors
Egocentric psychologic
conditions
Outgoing psychologic
conditions
Expectancy due to memory,
anticipation or prior conditioning
Distraction
Anxiety & fear Extraneous sounds, hypnosis,
mental absorption and
physical activities
Psychologic factors

54. Central
• Pain that
emanates from
the structures of
the CNS is felt
peripherally as
heterotopic pain
Projected
• Felt in the
peripheral
distribution of
the same nerve
that mediated
the primary
nociceptive
input
Referred
• Spontaneous
heterotopic pain
that is felt in an
area innervated
by a different
nerve than the
one that
mediates the
primary pain
I) Primary pain Secondary/Heterotopic pain
Site Source Site Source

55. Chief complaint Past medical history
Review of systems Psychologic
assessment

56. Location of pain
Onset of pain
Association with other
factors
Progression
Characteristic of pain
Quality of pain
Behaviour of the pain
Intensity
Concomitant symptoms
Flow of the pain
Aggravating and
alleviating factors
Physical modalities
Function & parafunction
Sleep disturbances
Medications
Emotional stress
Past consultation
and/or treatments
Relationship to other
complaints
Chief complaint

58.  Postoperative pain, postoperative dentin hypersensitivity and
discomfort (VAS). 56 patients who had CP
A split-mouth design: (SRP), (MWF), (Oresec) and (GV),
 No statistically significant differences between the patients'
discomfort levels. However, postoperative pain was
significantly higher for Oresec (P < .01) and GV (P < .05)
procedures than for SRP and MWF procedures
 Discomfort during periodontal treatments, postoperative pain
and postoperative dentin hypersensitivity were associated
significantly with age and type of therapy
Pain experienced by patients undergoing different
periodontal therapies. Canakçi CF, Canakçi V, 2007

59.  According to age, gender, and intersubject variation such as tooth
type, tooth surfaces or regions of mouth, probing depth, and bleeding
on probing
 VAS
 sites > 4 mm < 4 mm deep.
 No difference between genders
Pain levels in patients during periodontal probing and
mechanical non-surgical therapy. Canakci V, Canakci CF

60.  M= F
 Virtually all (97%) of the patients perceived periodontal treatment to
be associated with no more discomfort than conventional dental
treatment
Patient perceptions of periodontal therapy completed in a
periodontal practice. Fardal O, Johannessen AC, Linden GJ

61.  Pain control during nonsurgical periodontal therapy
Compendium of Continuing Education in Dentistry
(Jamesburg, N.J. : 1995) [2007, 28(12):666-9
 Fear of pain and discomfort during subgingival instrumentation
has been reported to deter nearly 10% of the population from
seeking treatment.
 Degree of periodontal pain experienced by the patient is
influenced by several factors, including amount of inflammation,
depth of the pockets, and location of the disease.
 Thus, timely elimination of inflammation is important not only in
treating the disease but also in preventing or controlling pain.

62.  Verbal Rating Scale (VRS)
 Melzack
 Simple, commonly used pain rating scale
 None
 Mild
 Discomforting
 Distressing
 Horrible
 Excruciating

63.  Visual Analog Scale (VAS)
 Sensitive to treatment effects
 Can be used with children

64. Mc Gill Pain Questionnaire (MPQ)
 Capture the multidimensional nature of pain and provide
quantitative measures of clinical pain
 Enables patients to choose from 78 adjectives (arranged in 20
groups)

65.  Sensory (groups 1 to 10)
 Affective (groups 11 to 15)
 Evaluative (group 16)
 Produce a Pain-Rating Index

66.  Observable Pain Behaviors
Behavior Observations
Guarding Abnormally slow, stiff, or interrupted movement
Bracing Stiff, pain-avoidant posturing while in static position
Rubbing Touching, rubbing, or holding of the painful area
Sighing Pronounced exhalation of air
Grimacing Obvious facial expression of pain
Keefe et al

67. Pain perception
Pain reaction
Psychophysiological process that represents the individual’s over manifestation
of the unpleasant perceptual experience. This aspect of pain embraces extremely
complex neuroanatomical and psychological structures
Physioanatomical process whereby an impulse is generated, following
application of an adequate stimulus & is transmitted to the CNS

68.  Emotional status
 Fatigue
 Age
 Racial and nationality characteristics
 Sex
 Fear & Apprehension

69.  Painful periodontal conditions include: NUG, herpetic
gingivostomatitis, periocoronitis
 Post operative pain: Mucogingival surgeries result in 6x more
pain and osseous surgeries 3.5x more discomfort than plastic
gingival surgery
 Common source of post operative pain: overextension of the
pack, prolonged exposure and dryness of bone, related to infection
(can cause lymphedenopathy), over production of heat etc

70.  Richard Bennet; Monheim’s Local Anesthesia And Pain Control In
Dental Practice-7th Edition
 Stanley F. Malamed; Handbook Of Local Anaesthesia-5th Edition
 Consice Medical Physiology, Chaudhuri, 5th Edition
 Gilbert H. Coffey, Melvyn V. Mahon. Pain: Theories And A New
Approach To Treatment.Journal of the national medical association
1982, Vol. 74, No. 2:147-153