PATHOPHYSIOLOGY OF PAIN

CONTENTS

• Introduction

• Definitions

• History

• Glossary

• Basic structure of a Neuron

• Stimulus and Receptors

• Dental and Pulpal pain

• Neurotransmitters

• Theories of Pain

• Fields subjective experience of Pain

• Pathways of Pain

• Pain modulation

• Classification of Pain

• Physiological pain vs Clinical pain

• Referred Pain

• Phantom Pain

• Summary

• References

• Pain is almost UNIVERSAL experience

• The mechanisms involved in pain sensation have been the object of considerable attention by neurophysiologists , physicians and pain’s unhappy victims

• Pain is difficult to define ,for pain is a SUBJECTIVE sensation

INTRODUCTION

• An unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described in terms of damage

IASP definition, Burket’s Oral Medicine 11th ed.

• The subject’s conscious perception of modulated nociceptive impulses that generate an unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Bell’s Orofacial Pain 5th ed.

DEFINITIONS

• Pain is defined as 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”.

Monhem’s Local anesthesia & pain control in dental practice. 7th ed

• A more or less localized sensation of discomfort ,distress, or agony resulting from the stimulation of specialize nerve endings.

Dorland’s Medical Dictionary

• An unpleasant sensation that is perceived as arising from a specific region of the body and is commonly produced by process that damage or are capable of damaging bodily tissue.

Fields

HISTORY

• Derived from Latin word - “Poena” meaning punishment from God

• Homer thought pain was due to arrows shot by God

• Aristotle, who probably was the first to distinguish five physical senses

considered pain to the “passion of the soul” that somehow resulted from the

intensification of other sensory experience

• Plato contented, pain and pleasure arose from within the body, an idea that

perhaps gave birth to the concept that pain is an emotional experience more

than a localized body disturbance.

• The Bible makes reference to pain not only in relationship to injury and

illness but also an anguish of the soul.

• Use of Willow bark & leaves by Hippocrates: Salicylic acid in

willow plant of genus Salix is the active ingredient of ASPIRIN

• Coca cola was initially sold as a cure for pain: concept of using

cocaine as a pain reliever.

• Queen Victoria was the first one to have anaesthesia for pain control

during childbirth

chloroform was used

GLOSSARY OF PAIN

Allodynia : pain due to non- noxious stimulus to normal skin.

Analgesia : absence of pain on noxious stimulation

Anaesthesia Dolorosa : pain in an area or region which is anaesthetic/

Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press Seattle, WA

Causalgia : a syndrome of sustained burning pain after a traumatic nerve lesion combined with vasomotor and sudomotor dysfunction and later trophic changes.

Central Pain : pain associated with a lesion of the central nervous system.

Dysaesthesia : an unpleasent abnormal sensation.

Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press Seattle, WA

Hyperalgesia : increased sensitivity to noxious stimulation.

Hyperaesthesia : increased sensitivity to stimulation, excluding special senses.

Hyperpathia : a painful syndrome, characterised by delay, over reaction and after sensation to a stimulus, especially a repetitive stimulus.

Hypoalgesia : diminished sensitivity to noxious stimulation.

Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press Seattle, WA

Hypoaesthesia : decreased sensitivity to stimulation, excluding special senses.

Neuralgia : pain in the distribution of a nerve or nerves.

Neuritis : inflammation of a nerve or nerves.

Neuropathy : a disturbance of function or pathological change in a nerve ; in one nerve, mononeuropathy; In several nerves, mononeuropathy multiplex;Asymmetrical and bilateral, polyneuropathy

Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press Seattle, WA

Nociceptor : a receptor preferentially sensitive to a noxious or potentially noxious stimulus.

Noxious : a noxious stimulus is a tissue damaging stimulus.

Pain threshold : the least stimulus intensity at which a subject persives pain.

Pain tolerance level : the greatest stimulus intensity causing pain that a subject is prepared to tolerate.

Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press Seattle, WA

BASIC STRUCTURE OF NEURON

Neurone transmits messages from the brain to a muscle or gland.

A sensory neuron is similar to a motor neuron except it has one long dendron and is designed to bring impulses to the brain.

STIMULUS

• A variety of stimuli are responsible for evoking pain.• These are ………. Mechanical tissue destruction

High tempt.Low PhChemical mediatorsHyper-osmotic solutions

• Sherrington all the stimuli capable of evoking pain are NOXIOUS as they are associated with actual or potential tissue injury.

• He postulated the existence of sensory receptors that sensed noxious agents (NOCICEPTORS)

• Hence perception of the pain also referred to as NOCICEPTION

RECEPTORS

FREE NERVE ENDINGS

C-FIBERSA-DELTAFIBERS

After receiving a nociceptive stimulus, two types of nerve fibers are stimulated.

A-d fibers ‘C’ fibers

Thick & finely myelinated. The thin & non myelinated.

Fast rate of conduction (15-20m/s).

Slower rate of conduction (0.5-2m/s).

Sensation due to the stimulation of A-d fibers is felt earlier than ‘C’ fibers.

Sensation due to the stimulation of ‘C’ fibers is felt after a long interval.

They conduct impulses to laminae I & V fibers.

They conduct impulses to laminae I & II of substantia gelatinosa

Dental and pulpal pain

NEUROTRANSMITTERS

• Neurochemicals that transmit

impulses across synaptic cleft

• Types:

• Small rapid-acting molecules

• Larger slower-acting molecules

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ACETYLCHOLINE- Most common

- Excitatory effect on postsynaptic neuron

NOREPINEPHERINE- Excitatory

neurotransmitter

GLUTAMATE- An amino acid

- Excitatory effect

ASPARTATE- An amino acid

- Excitation

SEROTONIN- A monoamine

released by platelets- Algogenic agent- Analgesic effect

GABA- Inhibitory effect on postsynaptic neuron

GLYCINE- Inhibitory transmittor

DOPAMINE- Inhibitory effect

HISTAMINE- Vasodilator

- Contraction of smooth muscle

RAPID-ACTING (SMALL MOLECULE) NEUROTRANSMITTERS

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SUBSTANCE P

• Released at central

terminals of primary

nociceptive neurons

• Acts as transport

substance

• Excitatory

neurotransmitter

• Action: rapid & short-

lived

ENDORPHINS

• Bind to morphine

receptors to obtund

pain

• Long lasting

• Antinociceptive

property

BRADYKININ

• Algogenic agent

• Excites all types of

receptors

SLOW-ACTING (LARGE MOLECULE) NEUROTRANSMITTERS

THEORIES OF PAIN

SPECIFICITY THEORY

DESCARTES 1664, MULER 1840

pain occurs due to stimulation of specific pain receptors (nociceptors) with transmission by nerves directly to the brain .

pain is purely an afferent sensory experience.

• PATTERN THEORY

GOLDSCHEIDER IN 1894 stimulus intensity and central summation are critical determinants of pain

particular patterns of nerve impulses that evoke pain are produced by summation of sensory input within the dorsal horn of spinal cord

pain results when total output of the cells exceeds a critical level….

for eg. touch+pressure+heat might add up in such a manner that pain is the modality experienced

GATE CONTROL THEORY:

Ronald Melzack and Patrick Wall proposed that a gating mechanism exists within the dorsal horn of the spinal cord.

Small nerve fibers (pain receptors) and large nerve fibers ("normal" receptors) synapse on projection cells (P), which go up the spinothalamic tract to the brain, and inhibitory interneurons (I) within the dorsal horn.

The interplay among these connections determines when painful stimuli reaches brain

When no input comes in, the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).

• Normal somatosensory input happens when there is more large-fiber stimulation (or only large-fiber stimulation).

• Both the inhibitory neuron and the projection neuron are stimulated, but the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).

• Nociception when there is more small-fiber stimulation or only small-fiber stimulation.

• This inactivates the inhibitory neuron, and the projection neuron sends signals to the brain informing it of pain (gate is open).

One byproduct of gate control theory was the introduction of Transcutaneous electrical nerve stimulation (TENS) as a therapeutic modality.

Descending pathways from the brain close the gate by inhibiting the projector neurons and diminishing pain perception.

FIELDS has described that the subjective experience of pain arises by 4 distinct process:

* Transduction * Transmission * Modulation * Perception

TRANSDUCTION: Process by which noxious stimuli lead to electrical activity in sensory nerve endings.

There are specialized sensory receptors distributed all over the body which respond to physical & chemical stimuli.

- Extroceptors - Proprioseptors

- Interoseptors

• Extroceptors are sensory receptors that are stimulated by the immediate external environment.

These receptors provide information from the skin and mucosa.

Egs1. Merkel’s corpuscles : tactile receptors in the submucosa of the

tongue and oral mucosa.2. Meissner’s corpuscles : tactile receptors in skin3. Ruffini’s corpuscles : pressure and warmth receptors4. Krause’s corpuscles or end bulbs : cold receptors5. Free nerve endings : perceives superficial pain and touch

• Proprioseptorsare sensory receptors that provide information from the musculoskeletal structures concerning the presence, position and movement of the body.

Egs 1. Pacinian corpuscles : receptors concerned in the preception of

pressure2. Periodontal mechanoreceptors : responds to biomechanical stimuli3. Free nerve endings : perceive deep somatic pain and other

sensation.

• Interoseptorsare sensory receptors that are located in and transmit impulses from the viscera (supply system) of the body.

Sensation from these receptors are involved in the involuntary functioning of the body.

Egs 1. Pacinian corpuscles : receptors concerned in the preception of

pressure.2. Free nerve endings : perceive visceral pain and other sensation.

• TRANSMISSION:neural events that carry the nociceptive input into the CNS

1) Peripheral Sensory Nerve : Primary afferent neuron- carries nociceptive input from the sensory organ (receptors) into the spinal cord.

2) Second Order Neuron- carries input to the higher centers through spinal cord.

3) Third Order Neuron- Interaction of neurons between the thalamus cortex and the limbic system as the nociceptive input reaches these higher centers.

MODULATION: - Ability of the CNS to control the pain transmitting neurons.

- Several areas of brain & cortex have been identified that can either enhance or reduce nociceptive input.

PERCEPTION: Reaching of the nociceptive input to the cortex is perception

It is at this level suffering & pain behavior begins.

PAIN PATHWAY

THE SPINAL CORD

• Traditionally it was thought that most pain fibers entered the dorsal root of the spinal cord (the "sensory" root) and then synapse in the dorsal part of the spinal gray matter, before passing the message up through the spinothalamic tract.

• It is now known that this is a gross oversimplification. In fact, anything up to 40% of sensory fibers enter in the ventral root!

• Histological the gray matter of the spinal cord is divided into ten 'laminae.by REXED

PATHWAYS OF PAIN SENSATION

Dorsal column medial leminiscal systemconveys touch, vibration and other non noscious stimuli ( not considered a pain pathway)

Ventrolateral system conveys noxious stimuli

Main ascending spinal pathways involved with relaying noxious stimuli to brain

spinothalamic spinohypothalamic spinoreticular spinomesenchephallic

PATHWAY OF PAIN SENSATION FROM VISCERA AND FACE

Thoracic&abdominal sympathetic nerves(thoracolumbar)

Oesophagus, trachea, larynx vagus& gloss pharyngeal nerves

Face trigeminal nerve

Pelvic sacral parasympathetic nerve.

DUAL TRANSMISSION OF PAIN TO CNS• All pain receptors are free nerve endings these endings use

two separate pathways for transmitting pain signals into CNS

• Two types of pathways are

1. A fast-sharp pain pathway ( neospinothalamic)

2. A slow-chronic pain Pathway (paleospinothalamic)

NEOSPINOTHALAMIC TRACT• A-delta fibers…mainly

mechanical and acute • Terminate in lamina I

(lamina marginalis) of the posterior dorsal horns.

• Excite second order neurons of neospinothalamic tract giving rise to long fibers that cross to opposite side through the anterior grey commissure and then pass upward to the brain stem in anteriolateral columns

• TERMINATION- in the reticular areas of the brain stem, but most pass all the way to thalamus, terminating in the ventro- basal complex along with dorsal column- medial lemniscal tract for tactile sensation.

• LOCALIZATION.- more exactly than slow pain

• NEUROTRANSMITTER- glutamate

PALEOSPINOTHALAMIC TRACT• c-fibers but to some extent

by a-delta fibers also.

• Peripheral fibers terminate in laminae II and III of the dorsal horns(SUBSTANTIA GELATINOSA).

• Then the signal pass through short fibers in dorsal horns and enter laminae V

• long axon arise & cross the anterior commissure to the opposite side of the cord, then upward to the brain in the anteriolateral pathway.

• NEUROTRANSMITTER – mainly substance-p and glutamate.

• Action of glutamate last for few milliseconds giving a faster pain or the 1st pain sensation

• Conversely sub-p is released slowly giving rise to more lagging or the 2nd pain sensation

• TERMINATION- only 1/10th to 1/4th of the fibers pass all the way to the thalamus ,instead they terminate in one of the following areas….

1. Reticular nuclei of medulla , pons and mesencephlon.2. The tectal area 3. Periaqueductal gray region

• LOCALIZATION- is poor, This is due to multisynaptic and diffuse connectivity of this

pathway.

PAIN MODULATION• The degree to which a person

reacts to pain varies tremendously.

• This results from capability of the brain to suppress inputs of pain signals to the nervous system by activating a pain control system c/a ANALGESIA SYSTEM OR THE DECENDING CONTROL PATHWAY

• This system consists of 3 components

1. The preaqueductal gray (PAG)and preventicular areas

2. The raphe magnus nucleus (RM)and

3. The nucleus reticularis paragigantocellular

• Electrical stimulation either in PAG(preaqueductal grey) or RM(raphe magnus) can completely suppress strong pain signals entering by way of dorsal horns

• neurotransmitters …enkephalins and serotonin

• produce both pre and post synaptic inhibition of incoming C and A-delta fibers

• Pre-synaptic inhibition….by blocking Ca- channels thus preventing the release of neurotransmitters

ROLE OF OPIATE SYSTEM IN MODULATION OF PAIN

• Morphine –derivative of opium causes analgesia by binding to the specific sites called the opiate receptors at the synapses of nociceptive pathways.

• This decreases nociceptive excitability, thus reducing the sensation of pain.

• Several such peptides are produced by the neurons that bind to the opiate receptor called the OPIATE PEPTIDES or ENDORPHINS (Endogenous Morphine Like Substances)

• Biologically active endorphins identified are… Beta-endorphin. gamma-endorphin, dynorphin, leu-enkephalin,

met-enkephalin.

• Produce both pre and post synaptic inhibition

• Nerve arising from PAG(preaquieductal grey) area secrete endorphins synapse with neuron in Raphe Magnus.

• The neurons arising from RM(Raphe Magnus) terminate dorsal horn serotonin which causes local neurons to secrete endorphins thus causing the inhibition of pain

CLASSIFICATION OF PAIN

• Nociceptive – somatic and visceral• Neuropathic • Psychogenic

NOCICEPTIVE PAIN

• Somatic• Activation of receptors in deep tissues• Aching, throbbing, gnawing• Opioid sensitive

• Visceral • Injury to sympathetically innervated organs abdominal

organs – • described as deep, colicky, paroxysmal

• NEUROPATHIC PAIN

• Injury to element of nervous system• Neuropathic Pain Presentations• Sensory loss• Sympathetic dysfunction• Hyperalgesia – increased response to a stimulus that is

normally painful• Allodynia – Pain caused by a stimulus that does not normally

provoke pain• Dysesthetic pain

• Burning • Tingling• Numbing• Squeezing• Pressing

PSYCHOGENIC PAIN

• Controversy surrounding labeling pain as wholly psychogenic

• Anxiety• Depression• Anger• Irritability, frustration

PHYSIOLOGICAL V CLINICAL PAIN

• Physiological pain• Pain can be differentiated from touch• protective function• warns of potential damage• transient• well localized• a defined stimulus response pattern

Clinical pain (pathological pain)

• elicited by A-delta as well as C fibers• associated with inflammation, neuropathy• associated with peripheral and central sensitization• pain outlasts duration of the stimulus• pain sensed in non-injured areas

Referred Pain

• DEFINITION: The pain sensation produced in some parts of the body is felt in other structures away from the place of pain development. It is called referred pain.

Deep and some visceral pain are referred to other areas

Superficial pain not reffered.

TRIGGER POINTS

• Regional myogenous pain condition characterized by local areas of firm, hypersensitive bands of muscle tissue known as trigger points.

• Trigger points are clinically identified as specific hypersensitive areas within

muscle tissue

• Active trigger points represent source of deep pain & produce referred pain

• If active referring trigger points are provoked

• Referral pain will be increased

• MASSETER :• Superficial layer refer to: post mandibular &

maxillary teeth, jaw, face.• Common complaint: tooth ache

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SOME TRIGGER POINTS AND THEIR REFERRAL PAIN

• TEMPORALIS :• All maxillary teeth• Upper face

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• LATERAL PTERYGOID:• TMJ area• Zygomatic area

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PHANTOM PAIN

• In general, Assume some one’s left superior extremity has been amputated at the level of middle of the arm.

• If now the exposed central stump of the nerve fibers be irritated, the fibers supposed to be coming from the fingers (which no longer exist now) may be irritated, and the subject feels as if the sensation is coming form the fingers (which no longer exist), thus he /she develops pain called the PHANTOM PAIN and the limb is called the PHANTOM LIMB

• In the dental literature, phantom pain felt in the tooth has been called atypical odontalgia.

• By definition atypical odontalgia means “ toothache of unusual cause”.

• Eg. Atypical odontalgia associated with neurogenic inflammation leading to secondary hyperalgesia.

Summary • Pain is both a sensory and emotional experience, and patients past experiences,

fears and anxieties can play an important role.

• Pain transmission is a result of complex peripheral and central processes. These processes can be modulated at different levels.

• Pain perception is a result of the balance between facilitatory and inhibitory interactions.

• Current areas of interest in pain research include investigating the effect of mood on pain processing in the brain and looking for novel drugs to block channels involved in pain transmission.

REFERENCES1. Orofacial pain- okeson2. Textbook of physiology- a k jain3. Textbook of medical physiology – guyton 11th edition4. Textbook of local anaesthesia-monheims5. International association for the study of pain:

http://www.Iasppain.Org/content/navigationmenu/generalresourcelinks/paindefinitions/default.Htm

6. Temporomandibular Disorders & Orofacial Pain. DCNA 2007; 51 (1)7. Merskey H, Bogduk N. 1994 Classifcation of Chronic Pain. IASP Press

Seattle, WA8. Medical problems in Dentistry. Scully & Cawson. 5th ed.

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Thank you