PAIN PATHWAYS AND ITS PHYSIOLOGY

CONTENTS Introduction Levels of pain processing 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 Methods of pain control Conclusion

INTRODUCTION

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

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

NEURAL PATHWAYS OF PAIN

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

NEUROANATOMY

FUNCTIONAL NEUROANATOMY

Distal terminals afferent nerves are specialized

sensory receptors

Called sensor-transducers or receptors

Classified in 3 main groups

Exteroceptors

Proprioceptors

Interoceptors

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

PROPRIOCEPTORS

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

FUNCTIONAL NEUROANATOMY

Periodontal ligament : Abundantly supplied by

sensory nerve fibers

Free nerve endings

Ruffini’s corpuscles : Apical area

Meissner’s corpuscles : Midroot region

Encapsulated spindle : Apex

INTEROCEPTORS

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

NOCICEPTORS

Responsible for identifying tissue injury

Free nerve ending : Non encapsulated branching of the axon

Receptive field: tissue area for which nociceptors responsible

Polymodal

C-fiber mechano/heat-sensitive nociceptors(CMH)-burning type A-fiber mechano/heat-sensitive

nociceptors(AMH)-pricking type

PATHWAYS OF PAIN SENSATION-FIRST ORDER NEURONS

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

PATHWAYS OF PAIN SENSATION

Second order neurons

Transmission neurons : Transfer impulse to the

higher centres

Ascend in the form of lateral spinothalamic tract

PATHWAYS OF PAIN SENSATION

3 different types of second order neurons

Low threshold mechanosensitive neurons (LTM)

• Light touch, pressure & proprioception

Nociceptive specific neurons (NS)

• Noxious stimulation

Wide dynamic range neurons (WDR)

• Wide range of stimulus intensities from non-noxious to noxious stimuli

PATHWAYS OF PAIN SENSATION

Dorsal horn of the spinal cord : Laminae

I to VI

Nociceptive input : Laminae I,II and V

PATHWAYS OF PAIN SENSATION

In the dorsal horn-Interneurons present : Transmit

impulses to other interneurons/Ascending neurons

Significant population of these interneurons in the

laminae II and III : Substantia gelatinosa

InhibitoryExcitatory

PATHWAYS OF PAIN SENSATION

Light touch and proprioception

Leminiscal systemAnt/Lat. STT

Pain,crude touch,temperature

PATHWAYS OF PAIN SENSATION

Paleospinothalamic tract

Neospinothalamic tract

PATHWAYS OF PAIN SENSATION

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

PATHWAYS OF PAIN SENSATION

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

NEUROPHYSIOLOGY OF PAIN

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

NEUROPHYSIOLOGY OF PAIN

Resting State

Resting potential : -70mV

Slightly permeable to Na+ ions

Freely permeable to K+ ions

Freely permeable to Cl- ions

Slow depolarization

Threshold / firing potential

Rapid depolarization

Repolarization

Depolarization : 0.3 msecRepolarization : 0.7 msec Entire process : 1 msec

NEUROPHYSIOLOGY OF PAIN

NEUROPHYSIOLOGY OF PAIN

Synapse

Interneuronal junctions

Presynaptic terminals : Small knobs

(on the surface of dendrites)

Synaptic cleft : 200 to 300Å in size

NEUROPHYSIOLOGY OF PAIN

Presynaptic terminals

Synaptic vesicles-Excitatory/inhibitory

Mitochondria

(has ATP -synthesize new transmitter substances)

Chemical synapseElectrical synapse

Some smooth & cardiac muscles

NEUROPHYSIOLOGY OF PAIN

Receptor protein and Ionophore component

NEUROPHYSIOLOGY OF PAIN

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

NEUROTRANSMITTERS

Rapid-acting neurotransmitters

Excitatory agentsAcetyl choline, Norepinephrine,

Glutamate, Aspartate, Histamine, Nitric Oxide

Inhibitory agentsSerotonin, Gamma Amino

Butyric Acid (GABA),Glycine, Dopamine

Slow-acting neurotransmitters(Neuropeptides)

Excitatory agentsSubstance P, Bradykinin

Inhibitory agentsEndorphins

NEUROPHYSIOLOGY OF PAIN

Elimination of the transmitter from the synapse

Diffusion

Enzymatic destruction

Re-uptake

NEUROPHYSIOLOGY OF PAIN

NEUROCHEMISTRY OF NOCICEPTION

Peripheral nociceptors Thermal stimulation Mechanical stimulation Chemical stimulation

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

Damage to tissue cells : Leakage of intracellular contents

Potassium and histamine : Activate or sensitise the nociceptors

Arachidonic acid:LT and 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

THEORIES OF PAIN

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

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

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 pt with trigeminal neuralgia exhibits pain from the stimulus no greater than general touch.

THEORIES OF PAIN

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

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.

THEORIES OF PAIN

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 cells Dr. Ronald Melzack Dr. Patrick Wall

THEORIES OF PAIN

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

THE MODULATION CONCEPT

Gate control theory

Neural impulses : Modulated as they ascend to

higher centre

Facilitation : Impulses Accentuate pain

experience

Inhibition : Impulses Lessen pain

experience

PAIN MODULATION

Pain modulation : Various levels of the CNS

Trigeminal spinal tract nucleus

Reticular formation

Descending inhibitory system

Psychologic modulating factors

PAIN MODULATION

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

PAIN MODULATION

Clinical relevance

Individual touches a hot stove : Nociceptive reflex

Immediately withdraws the hand

Rapidly wave the hand from side to side : Pain is reduced

or even eliminated

C-fiber input carrying the nociception is inhibited “Gated

out” by the A-β fiber input associated with the motion

Counter stimulate the injured area to reduce pain

PAIN MODULATION

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

PAIN MODULATION

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

PAIN MODULATION

 Descending Inhibitory System

Dorsal root ganglion cells : Initiate sensory

impulses

Arousal system

Neural mechanism in the brainstem that balance

this continuous barrage of sensory input

Orthodromically-root Antidromically-

peripheral nerve

PAIN MODULATION

Affect all sensory input

ascending into brainstem

Analgesic system( 3 parts):

Periaqueductal(PAG)

Nuclues Raphes Magnus(NRM)

Descending neurons

Affects nociceptive input

PAIN MODULATION

 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

PAIN MODULATION

 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)

Applied at specific sites where electrical impedance is

low & deeper nociceptors are available to be stimulated

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

TYPES OF PAIN

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

PAIN EVALUATION

Chief complaint

Review of systems

PAIN EVALUATION

Location of pain

Onset of pain

Association with other factorsProgression

Characteristic of pain Quality of pain Behaviour of the pain Intensity

Concomitant symptoms Flow of the pain

Past consultation and/or treatments

Chief complaint

MEASUREMENT OF PAIN

Verbal Rating Scale (VRS)

Melzack

Simple, commonly used pain rating scale None Mild Discomforting Distressing Horrible Excruciating

MEASUREMENT OF PAIN

Visual Analog Scale (VAS)

Sensitive to treatment effects Incorporated into pain diaries Can be used with children

Postoperative pain, postoperative dentin hypersensitivity and discomfort (VAS). 56 patients who had CP.

A split-mouth design: (SRP), (MWF), (OF) and (GV),

No statistically significant differences between the patients' discomfort levels. However, postoperative pain was significantly higher for OF (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

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.

The highest mean score was recorded for anesthesia in the

upper anterior region.

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.

MEASUREMENT OF PAIN

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)

MEASUREMET OF PAIN

Sensory (groups 1 to 10)

Affective (groups 11 to 15)

Evaluative (group 16)

Produce a Pain-Rating Index

MEASUREMENT OF PAIN

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

DUAL NATURE OF PAIN

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

FACTORS AFFECTING PAIN

Emotional status

Fatigue

Age

Racial and nationality characteristics

Sex

Fear & Apprehension

METHODS OF PAIN CONTROL

Removing the cause

Blocking pathway of painful impulses

(most widely used in dentistry-L.A)

Raising pain threshold (Analgesics)

Preventing pain reaction

by cortical depression (G.A)

Using psychosomatic method

Pain Perception

Pain Reaction

Pain Perception & Reaction

PERIODONTAL PAIN Painful periodontal conditions include: NUG, herpetic

gingivostomatitis, periocoronitis

Postop pain: Mucogingival surgeries result in 6x more pain and osseous surgeries 3.5x more discomfort than plastic gingival surgery

Common source of postop pain: overextension of the pack, prolonged exposure and dryness of bone, related to infection (can cause lymphedenopathy, elevation in temp)

REFERENCES

Jeffrey P. Okeson; Bell’s Orofacial Pains-6th Edition

Richard Bennet; Monheim’s Local Anesthesia And Pain Control In Dental

Practice-7th Edition

Stanley F. Malamed; Handbook Of Local Anaesthesia-5th Edition

Greenberg, Glick; Burket’s Oral Medicine Diagnosis & Treatment-10 th

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

Thank you