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PAIN AND PAIN PATHWAYS

Presented by:

Dr. Dhwani Gohil

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"I don't accept the maxim 'there's no gain without pain', physical or

emotional. I believe it is possible to develop and grow with joy rather than grief. However, when the pain comes my way, I try to get the most growth

out of it." ~ Alexa McLaughlin

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CONTENTS • Introduction• Definition• History• Incidence• Related Terms• Characteristics of pain• Classification• Pain receptors• Neural pain pathways• Sensory neurons• Peripheral mechanism of injury induced pain• Theories of pain• Pain pathways

Dual pain pathwayPain pathway of Maxillofacial Region

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• Modulation of pain

• Factors affecting pain

• Visceral pain • Referred pain

• Phantom limb pain • Inhibition of pain • Diagnosis • Treatment • Conclusion

• References

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INTRODUCTION

• Pain is a sensory experience of special significance to physicians and basic scientists.

• Pain is the commonest symptom which physicians are called upon to treat.

• Apart from its obvious applied value, study of physiology of pain has taught us a lot about neural function in general.

• Pain is an intensely subjective experience, and is therefore difficult to describe.

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• But it has two features which are nearly universal. First, it is an unpleasant experience; and secondly, it is evoked by a stimulus which is actually or potentially damaging to living tissues.

• That is why, although it is unpleasant, pain serves a protective function by making us aware of actual or impending damage to the body.

• Like all sensory experiences, pain has two components, the first component is the awareness of a painful stimulus and the second is the emotional impact (or effect) evoked by the experience.

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• While the awareness is localized to the area stimulated, the experience involves the whole being.

• That is why even when only a finger is hurt, the whole person suffers.

• The two components of pain also imply that the same painful experience may evoke widely different degrees of suffering in different persons, and even in the same person under different circumstances.

• From a physiological point of view, there are two types of pain. One, ‘fast pain’, is conducted by faster conducting myelinated fibers, is well localized, and is sharp or pricking in character. The other, ‘slow pain’ is conducted by slower – conducting unmyelinated fibers, is poorly localized, and is burning or dull and aching in character.

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The International Association for the Study of Pain

Pain is "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage"

• Monheim : “An unpleasant emotional experience usually initiated by noxious stimulus and transmitted over a specialized neural network to the CNS where it is interpreted as such.”

DEFINITION OF PAIN

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HISTORY

• Derived from Latin -“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.

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• 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.

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INCIDENCE OF PAIN

According to Cohen – It was found that 21.8% of adult in the United States experience orofacial pain symptoms within 6 months of study.

The most common pain was toothache, which was estimated to have occurred in 12.3% of the population

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RELATED TERMS

Allodynia

Hyperalgesia & hypoalgesia

Hyperesthesia & hypoesthesia

Hyperpathia

Causalgia

Neuralgia

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CHARECTERISTICS 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.

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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.

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CLASSIFICATION OF PAIN

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.

Deep (from muscles/bones/fascia/periosteum) e.g. fractures/arthritis/fibrositis, rupture of muscle belly

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• Fast pain within 0.1 sec• Slow pain after 1 sec or more : Associated with tissue destruction

PRACTICAL CLINICAL CLASSIFICATION OF CARNIO - FACIAL PAIN

General Classification

Origin of Pain Quality of Pain

Extra cranial Structure

Craniofacial region Varies

Referred pain from remote pathologic

sites

Distant organs and structures

Aching and pressing

Intracranial pathosis

Brain and related structures

Varies

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Neurovascular Blood Vessels Throbbing, pulsing or pounding

Neuropathic Sensory nervous system

Shooting, sharp, burning pain

Causalgic Sympathetic nervous system

Burning

Muscular Muscles Deep aching, tight

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It can be also classified as :-

Typical Pain Disorders Atypical Pain Disorders

PeriodontalgiaNeuralgic (trigeminal neuralgia) Vascular (migraine, cluster headache) Otic (Otitis media)Sinus (Sinusitis)Heart (cariogenic jaw pain) Salivary gland DisorderMusculo skeletal disorder

Causalgia Reflex sympathetic dystrophyAtypical facial painPhantom tooth painNeuralgia including cavitational osteonecrosis

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PAIN RECEPTORS

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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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SENSORY RECEPTORS

GENERAL

SENSES

SPECIAL

SOMATIC VISCERAL

SUPERFICIAL DEEPTouch-pressureThermalPain

Pain Proprioception

PainBaroreceptionChemoreception

VisualAuditionOlfactionGustation

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Cutaneous Receptors:

The perception of different kinds of sensation has demonstrated the existence of sensory spots in the skin. These sensory spots are thought to contain receptors which are distinguished by the form of stimulus that excites them and their location within the skin, and are distinguished morphologically as corpuscular and noncorpuscular.

The pacinian corpuscles, in particular, are highly sensitive mechanoreceptors which respond to rapid mechanical changes, and are especially responsive to vibration. Other mechanoreceptors are the Meissner corpuscles, Golgi – Mazzoni corpuscles, Ruffini’s ending and Krause bulb.

Although, electron microscopy has defined the presence of many receptors structurally, functionally three categories of cutaneous receptors are thought to exist: mechanoreceptors, thermo receptors, and nociceptors.

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A nerve ending that responds to noxious stimuli that can actually or potentially produce tissue damage.

Free nerve endings i.e., they are not enclosed in a capsule. 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.

These substances include histamine, serotonin, bradykinin, acetylcholine, potassium ions and hydrogen ions. It is possible that noxious mechanical and thermal stimuli also act through the release of some of these chemicals.

NOCICEPTORS

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Since pain receptors respond to a wide variety of stimuli, they are called polymodal.

Types of nociceptors :

Aδ Mechanical Nociceptors

C Polymodal Nociceptors

C fibre mechanical nociceptors

High threshold cold nociceptors

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MechanoreceptorsMechanoreceptors, which respond to tactile non painful stimuli, can be

assessed psychophysically by the ability of a human subject to discriminate whether application of a two blunt-point stimuli is perceived as one or two points.

These receptors are divided into two functional groups (rapidly or slowly adapting) depending on their response during stimuli.

Rapidly adapting mechanoreceptors respond at the onset and offset of the stimuli, while slowly adapting mechanoreceptors respond throughout the stimuli duration.

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Mechanoreceptors can be divided into those expressed in:

Hairy skin (hair follicle receptors):

Low threshold, rapidly adapting.

Three major subtypes: ‘down’, ‘guard’, tylotrich’.

Glabrous (hairless) skin:

Small receptive fields.

Two major subtypes: ‘Meissener’s capsule’ (rapidly adapting) and ‘Merkel’s disc’ (slowly adapting).

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Proprioception (limb position sense), 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).

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C – fibre mechano heat sensitive nociceptors

These fibres are considered polymodal, as they respond to mechanical, heat, cold and chemical stimuli.

Their monotonic increase in activity evokes a burning pain sensation at the thermal threshold in humans (41–49°C).

CMH responses are affected by stimuli history and are subject to fatigue and sensitization modulation.

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A-fibre mechano-heat-sensitive nociceptors

Activation of these receptors is interpreted as sharp prickling or aching pain. Owing to their relatively rapid conduction velocities (5–36 m/s), they are responsible for first pain. Two subclasses of AMHs exist: types I and II.

Type I fibres respond to high magnitude heat, mechanical and chemical stimuli and are termed polymodal AMHs. They are found in both hairy and glabrous skin.

Type II nociceptors are found exclusively in hairy skin. They are mechanically insensitive and respond to thermal stimulation in much the same way as CMHs (early peak and slowly adapting response) and are ideally suited to signal the first pain response.

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Deep tissue nociceptorsUnlike cutaneous pain, deep pain is diffuse and difficult to localize, with no

discernable fast (first pain) and slow (second pain) components. In many cases deep tissue pain is associated with autonomic reflexes (e.g. sweating, hypertension and tachypnoea).

Units that do not respond to mechanical stimuli have been termed silent nociceptors. Silent nociceptors are also present within the viscera. Silent visceral afferents fail to respond to innocuous or noxious stimuli, but become responsive under inflammatory conditions.

Visceral afferents are mostly polymodal C- and A-fibres.

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Aß - fibres Aδ - fibres C- fibres

Threshold Low Medium High

Axon diameter 6-14μm 1-6μm 0.2-1μm

Myelination Yes Thinly No

Velocity 36-90 5-36 0.2-1

Receptor types Mechanoreceptor Mechano/Nociceptor

Nociceptor

Receptive field Small Small Large

Quality Touch Sharp/first pain Dull/second pain

Summary of receptor types

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NEURAL PAIN PATHWAYS

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Nociception is the neural mechanism by which an individual detects the presence of a potentially tissue harming stimulus. There is no implication of (or requirement for) awareness of this stimulus.

The nociceptive mechanism (prior to the perceptive event) consists of a multitude of events as follows:

Transduction:

This is the conversion of one form of energy to another. It occurs at a variety of stages along the

nociceptive pathway from:

– Stimulus events to chemical tissue events.

– Chemical tissue and synaptic cleft events to

- Electrical events in neurones.

– Electrical events in neurones to chemical events at synapses.

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Transmission:

Electrical events are transmitted along neuronal pathways, while molecules in the synaptic cleft transmit information from one cell surface to another.

Modulation:

The adjustment of events, by up- or down regulation. This can occur at all levels of the nociceptive pathway, from tissue, through primary (1°) afferent neurone and dorsal horn, to higher brain centres.

Thus, the pain pathway as described by Descartes has had to be adapted with time.

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SENSORY NEURONS

First Order Second Order Third Order

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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.

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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.

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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.

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Third Order Neuron

Cell bodies of third order neurons of the nociception-relaying pathway are housed in: the ventral posterior lateral, the ventral posterior inferior, and the intralaminar thalamic nuclei

Third order neuron fibers from the thalamus relay thermal sensory information to the somesthetic cortex.

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PERIPHERAL MECHANISMS OF INJURY INDUCED OR INFLAMMATORY PAIN

Nociceptor activation is dynamically modulated by the magnitude of stimuli. Therefore, it is not surprising that supra-threshold or tissue-damaging stimuli alter subsequent nociceptor responses.

Overt tissue damage, or inflammation, causes the sensation of pain.

The most common symptom of on-going or chronic pain states is tenderness of the affected area. This tenderness, or lowered threshold for stimulation-induced pain is termed hyperalgesia.

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Hyperalgesia, or lowered-threshold to thermal and mechanical stimuli, occurs at the site of trauma (primary hyperalgesia).

Uninjured tissue around this area also becomes sensitized, but to mechanical stimuli only (secondary hyperalgesia or allodynia).

Peripheral sensitization mediates primary hyperalgesia to thermal stimuli. Campbell and Meyer illustrated that CMHs become sensitized to burn injuries in hairy skin, but fail to do so in glabrous skin, where AMH become sensitized for heat hyperalgesia.

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Sensitization of nociceptors: inflammation

Tissue injury results in complex sequelae procured in part by the recruitment of inflammatory mediators. The inflammatory reaction rapidly proceeds in order to remove and repair damaged tissue after injury. Pain develops in order to protect the organism from further damage. The affected area typically becomes:

Red (rubor).

Hot (calor): as a result of increased blood flow.

Swollen (tumor): due to vascular permeability.

Functionally compromised (function lasea).

Painful (dolor): as a result of activation and sensitization of primary afferent nerve fibres.

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Sensitization occurs due to the release of chemical inflammatory mediators from damaged cells.

A number of mediators directly activate nociceptors, while non-nociceptive afferents remain unaffected.

Others act on local microvasculature causing the release of further chemical mediators from mast cells and basophils, which then attract additional leucocytes to the site of inflammation.

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NEUROCHEMISTRY OF NOCICEPTIVE PAIN

The peripheral nociceptor can be activated by thermal, mechanical, and chemicals stimulation.

When thermal and mechanical stimulation produce nociceptive input, the reason for the pain is usually apparent.

There are a variety of compounds that can accumulate near the nociceptor following tissue injury that can be responsible for maintaining nociceptive input.

There are at least three sources of these compounds: the damaged cells themselves, secondary to plasma extravasation and lymphocyte migration, or the nociceptor itself.

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Damage to tissue cells produces leakage of intracellular contents. Among the substances released by tissue damage are potassium and histamine, both of which either activate or sensitize the nociceptor.

These substances have been documented to excite polymodal nociceptors and produce pain when injected into skin. Other compounds such as acetylcholine, serotonin, and ATP maybe released by tissue damage and are known to either activate or sensitize nociceptors.

Bradykinin one of the most potent pain producing substances that appears in injured tissue. Bradykinin is an endogenous polypeptide consisting of a chain of nine amino acids.

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Released as part of an inflammatory reaction, it is a powerful vasodilator and causes increased capillary permeability.

Bradykinin requires the presence of prostaglandins act. It is also released during ischemic episodes. Polymodal nociceptors can be activated by bradykinin and they then can become sensitized to thermal stimuli.

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.

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Prostaglandin E2 is metabolized from arachidonic acid through the action of cyclo – oxygenase. This occurs in conjunction with an inflammatory process.

Prostaglandins do not seem to be algogenic substances per se. They sensitize nociceptive nerve endings to different type stimuli, thus lowering their pain thresholds to all kinds of stimulation.

Prostaglandins are required for bradykinin to act, bradykinin in turn stimulates the release of prostaglandins.

The two are therefore naturally potentiating.

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In addition to the chemical mediators that are released from damaged cells or synthesized in the region of damage, the nociceptors themselves can release substances that enhance nociception.

One such substance is substance P. and, when stimulated, can release this potent excitatory neurotransmitter into the extra cellular space.

Substance P is a very strong vasodilator and produces edema. Substance P also causes release of histamine from mast cells, which is an excitatory neurotransmitter and also causes vasodilatation and edema.

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THEORIES OF PAIN

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It is often assumed that pain is a warning that damage has occurred. But this is not strictly true.

Because pain may occur when there is no obvious disease as in primary neuralgias and many diseases does not cause pain, at least in the early stages.

So these are various theories being put forward on how nerve impulses give rise to sensation of pain.

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INTENSITY THEORY

According to this view, pain is produced when any sensory nerve is stimulated beyond a certain level.

In other words pain is supposed to be a non-specific sensation and depends only on high intensity stimulation.

But the trigeminal system provides an example against this theory. In case of trigeminal neuralgia the patient can suffer excruciating pain from a stimulus no greater than a gentle touch provided it is applied to a trigger zone.

Although, the intensity theory is not accepted, it remains true to say that intensity of stimulation is a factor in causing pain.

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Specificity Theory (Johannes Muller, 1842):

According to this view, pain is a specific modality equivalent to vision and hearing etc.

Just as there are Meissner corpuscles for the sensation of touch, Ruffini end organs supposedly for warmth and Krause end organs supposedly for cold, so also pain is mediated by free nerve endings.

Certain psychophysical studies have been regarded as supporting specificity theory. Specialization is known to exist in nervous system and there are well known tracts.

But concept of specific nerve ending is no long tenable. The Krause and Ruffini endings are absent from the dermis of about all hairy skin, so it is certain that these structures cannot be receptors for cold and warmth.

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Protopathic and Epicritic theory:

Head and Rivers (1908) postulated the existence of two cutaneous sensory nerves extending from the periphery to the CNS.

The protopathic system is primitive, yielding diffuse impression of pain, including extremes of temperature and is upgraded.

The epicritic system is concerned with tough discrimination and small changes in temperature and is phylogenetically a more recent acquisition.

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Pattern theory (Goldscheider, 1894):

This theory states that pain sensation depends upon spatio – temporal pattern of nerve impulses reaching the brain.

According to Woddell (1962) warmth, cold and pain are words used to describe reproducible spatio – temporal pattern, or codes of neural activity evoked from skin by changes in environment.

The precise pattern of nerve impulse entering the CNS will be different for different regions and will vary from person to person because of normal anatomical variations.

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Gate Control Theory

This theory proposed by Melzack and Wall in 1965 and recently re-evaluated is receiving considerable attention.

This theory of pain takes into account the relative in put 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.

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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.

Large diameter fibers transmit signals that are initiated by pressure, vibration and temperature; small diameter fibers transmit painful sensations.

Activation of large fiber system inhibits small fiber synaptic transmission, which closes the gate to central progression of impulse carried by small fibers.

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PAIN PATHWAYS

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From the site of pain generation, i.e. 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.

From the SGR, next order ( i.e. 2nd order) neuron arises, crosses to the opposite side, then moves up through the white matter of spinal cord to reach the brain.

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i) Most of these 2nd order neurons travel up as spinothalamic tract (STT), then ultimately terminate in the proper area of thalamus, from these specific nuclei of thalamus, next order neurons arise to terminate on the cerebral cortex, at areas SI & SII as well as cingulate gyrus (which is the key area for production of some emotions).

At SGR, there is a synapse between 1st order & 2nd order neuron. Also there is synapse of 2nd & 3rd order neuron at thalamus.

The NT (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.

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Other 2nd order neurons, from SGR also are known, & they also cross to the opposite side to reach different areas of brain.

The tip of dorsal horn, particularly the SGR plays a key role in modification of pain perception. It is called a gate. As a gate can be shut/ partially opened/ fully opened to control incoming traffic, so also behaves the SGR controlling the incoming traffic of pain.

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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.

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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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Axons of secondary neurons emerge from the spinal nucleus, cross the midline and ascend to join fibers of mesencephalic nucleus to form trigeminal lemniscus or spinothalamic tract of 5th nerve.

These tracts continue upward and terminate in the postero ventral nucleus of thalamus. From here it is transmitted to posterocentral convolutions of cortex.

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Pain pathway of Maxillofacial Region

5th cranial nerve or trigeminal nerve is principal sensory nerve of head region.

Any stimulus in area of trigeminal nerve is first received by both myelinated and non-myelinated fibers, and conducted as an impulse along afferent fibers of ophthalmic, maxillary and mandibular branches into semilunar or gasserian ganglion.

Pain impulse descends from the pons by spinal tract fibers of trigeminal nerve through the medulla.

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FAST PAIN & SLOW PAIN

Fast Pain

Also known as Sharp pain, pricking pain or acute pain.

Easily localized.

Not felt in the deep visceral organs.

Slow Pain

Also known throbbing pain, aching pain or chronic pain.

It can occur both in skin and in almost any deep tissue or organ.

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The three main types of stimuli for pain are mechanical, thermal and chemical. Fast pain is elicited by mechanical and thermal types of stimuli, whereas slow pain can be elicited by all three types.

Some of the chemicals that excite the chemical type of pain are bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine and substance P and also prostaglandin.

Chemical substances are especially important in stimulating the slow, suffering type of pain that occurs after tissue injury.

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MODULATION OF PAIN

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Noxious stimuli of comparable intensity may produce varying degrees of pain in the same individual under different circumstances.

For example, an injury acquired by an athlete in the sports field or by a soldier in the battlefield is less painful than a comparable injury suffered in a road accident.

In other words, pain can be modulated.

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In the 1960s neurophysiological studies provided evidence that the ascending output from the DH of the spinal cord following somatosensory stimulation depended on the pattern of activity in different classes of 1° sensory neurones. Melzack and Wall proposed the ‘gate control’ theory of pain.

It suggested that activity in low-threshold, myelinated 1° afferents would decrease the response of DH projection neurones to nociceptive input (from unmyelinated afferents). Although there has been controversy over the exact neural substrates involved, the ‘gate control’ theory revolutionized thinking regarding pain mechanisms.

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Pain is not the inevitable consequence of activation of a specific pain pathway beginning at the C-fibre and ending at the cerebral cortex.

Its perception is a result of the complex processing of patterns of activity within the somatosensory system.

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FACTORS AFFECTING PAIN

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1. Emotional status:

The pain threshold depends greatly on attitude towards the procedure. In case of emotionally unstable and anxiety patient the pain threshold is low but reaction is high.

2. Fatigue:

Pain reaction threshold is high in subjects who has good night sleep and relaxed, then those persons who are tired.

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3. Age :

Older individuals tend to tolerate pain and thus have higher pain reaction threshold than young individuals. Perhaps their philosophy of living or the realization that unpleasant experiences are a part of life may account for this fact.

4. Racial and nationally characteristics:

It has been said that racial characteristics are reflected in the pain. The Caucasian and Negro races have little or no variation in the pain reaction threshold.

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The Latin Americans and Southern Europeans are more emotional than North Americans or Northern Europeans may be in warmer climates tend to have lower pain reaction threshold.

5. Sex :

Men have higher pain threshold than women. This may be a reflection of man’s desire to maintain his feeling of superiority and this is exhibited in his pre determined effort to tolerate pain.

6. Fear and apprehension:

Most cases pain threshold is lowered as fear and apprehension increases. Individuals who are extremely fearful tend to magnify their experiences.

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VISCERAL PAIN

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A striking characteristic of the brain is that although it receives and processes nociceptive information, the brain itself has no sensation of pain.

The internal (visceral) organs themselves have no pain receptors, pain receptors are present embedded in the walls of the arteries serving these organs.

Visceral pain is characterized as diffuse and poorly localized and is often “referred to” and felt in another somatic structure distant or near the source of visceral pain.

Nociceptive signals from the viscera generally follow the same pathway as signals arising from somatic structures.

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General visceral afferent nociceptive information from visceral structures of the trunk is carried mostly by type C, Aδ, or Aβ fibers.

Visceral pain signals relayed to the primary somatosensory cortex may be associated with referred pain to a somatic structure.

In addition to projections to the somatosensory cortex, recent studies indicate that nociceptive signals are also relayed to the anterior cingulate and anterior insular cortices, two cortical areas implicated in the processing of visceral pain.

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REFFERED PAIN

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Pain occurring in a visceral structure is usually not felt in the viscus itself but on the surface of the body or in some other somatic structure that may be located quite some distance away. Such type of pain is said to be referred pain.

It is commonly observed in all type of deep pain both visceral and somatic pain e.g. the pain of angina pectoris is often felt in the left arm or the jaw and diaphragmatic pain is often felt in the shoulder or neck.

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It is not accentuated by provocation of the site where the pain is felt, it is accentuated only by manipulation of the primary pain source.

It is dependent on continuance of the primary initiating pain, it ceases immediately if the primary pain is arrested or interrupted.

Anesthesia of the structure where the referred pain is felt does not arrest the pain. It should be noted that although the primary initiating pain is of the deep visceral type, the secondary referred pain may be felt in either deep or superficial structures.

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The two most popular theories explaining mechanism of referred pain are

Convergence Projection Theory

Convergence Facilitation Theory

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Convergence-Projection Theory

The sympathetic afferent fibers carrying the pain sensation emerges from the viscus and via dorsal root ganglion ends in the posterior horn of the spinal cord.

Afferent somatic nerve, emerging from the pain receptor, of the corresponding dermatome of the viscus, enters the same segment and terminates on the very same cell where sympathetic nerve is terminating i.e. these two different neurons converge on the same next order neuron.

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Therefore when the next order neuron is stimulated – the impulse reaches the brain and person feels pain, but he feels as if the pain is coming from the dermatome.

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Convergence Facilitation Theory

According to this theory, nociceptive input from the deeper structure causes the resting activity of the second order neurons pain transmission in the spinal cores to increase or be facilitated.

The resting activity is normally created by impulses from the cutaneous afferents, facilitation from deeper nociceptors causes the pain to perceived in the area that creates the normal, resting background activity.

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The theory tries to incorporate the clinical observation that blocking sensory input from the reference area with either L.A. or cold, can sometimes reduce the perceived pain e.g. in myofacial pain, application of a vapocoolant spray is actually a popular and effective modality used for pain control.

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Subliminal Fringe Effect

The afferent sympathetic nerve bringing pain sensation from the viscus terminate on the second order neuron, but at the same time it also via collateral, stimulate another second order neuron.

This second order neuron is synapsed with somatic neuron of the corresponding dermatome.

Therefore, when the pain is felt by the patient, he feel as if the pain is coming from the corresponding dermatome.

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When pain is referred, it is usually to a structure that developed from the same embryonic segment or dermatome as the structure in which the pain originate. This is called dermatome rule e.g. during embryonic development the diaphragm migrates from neck region to the adult location between the chest and abdomen and take its nerve supply, the phrenic nerve with it.

One third of the fibers in the phrenic nerve are afferent and they enter the spinal cord at the level of IInd to IV the cervical segments, the same location at which afferents from the tip of the shoulder enter.

Dermatome Rule

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Referred pain does not occur haphazardly but in fact follows three clinical rules,

1) Referred pain frequently occurs within a single nerve root, passing from one branch to another. E.g.. Mandibular molar presenting with a source of pain will commonly refer pain to a maxillary molar. This is fairly common occurrence with dental pain. Generally, if the pain is referred to another distribution of the same nerve, it does so in a laminated manner. This lamination follows dermatomes. Trigeminal lamination patterns are determined by the manner in which the primary afferent neurons enter in the spinal tract nucleus. According to Kunc, the location of the trigeminal nociceptive terminals within the nucleus caudalis is as follows:

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a) Fibers from parts near the saggital midline of the face terminate highest in the nucleus (cephlad).

b) Fibers from parts located more laterally terminate lowest in the nucleus (cauded).

c) The intermediate fibers terminate intermediately in the nucleus.

This grouping of the terminals of the primary trigeminal neurons should influence the location of clinical effects of central excitation, a molar tooth projects dorsal to canine projects dorsal to an incisor, which confirms the vertical lamination just cited. This means incisors refer to incisors, premolars to premolars, and molars to molars on the same side of the mouth. In other words, molars do not refer pain to incisors or incisors to molars.

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2) The referred pain in the trigeminal area rarely crosses the midline unless, it originates at the midline. For example, pain in the right temporomandibular joint will not likely cross over to the left side of the face nor will right molar pain refer to a left molar. This is not true in the cervicospinal region or below, cervicospinal pain can be referred across the midline, although it normally stays on the same side as the source.

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3) If referred pain is felt outside the nerve that mediates the pain, it is generally felt cephalad to the nerve (upward, toward the head) and not caudally. Clinically this means that deep pain felt in the sacral area maybe referred to the lumbar area, as well as lumbar to thoracic, thoracic to cervical, and cervical to trigeminal.

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PHANTOM LIMB PAIN

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Individuals who have had a limb amputated may experience pain or tingling sensations that feel as if they were coming from the amputated limb, just as if that limb were still present.

Although the mechanism of phantom limb pain is not understood, the following two possible explanations are offered.

1) If a sensory pathway is activated anywhere along its course, nerve impulses are generated that travel to the CNS where they initiate neural activity. This neural activity ultimately “creates” sensations that feel as though they originated in the nonexistent limb.

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2) Another possibility is that since there is no touch, pressure, or proprioceptive information transmitted to the CNS from the peripheral processes of the sensory neurons that initially innervated the amputated limb, there are no impulses from touch fibers to attenuate the relaying of nociceptive impulses to the nociceptive pathways, enhancing nociceptive transmission and pain sensation. Since nociception is not as localized, cortical areas corresponding to the phantom limb will be activated.

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INHIBITION OF PAIN

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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. The purpose of surgical treatment is to interrupt the pain impulse somewhere between receptors and innervation centers of brain, by severing the sensory nerve, its spinal root or certain tracts in spinal cord or brain.

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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.

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Newer Approaches

Transcutaneous Neural Stimulation (TNS)

With TNS, 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.

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Acupuncture (ACUS = NEEDLE, PUNGERE = STING)

Method of inhibiting pain impulses.

Acupuncture theory is based on an invisible system of communication between various organs of the body that is distinct from circulatory, nervous and endocrine system.

Needles are inserted through selected areas of skin and then twirled.

After 20-30 minutes, pain is deadened for 6-8 hours

Location of needle insertion depends on part of body acupuncturist wishes to anesthetize.

Example : to pull a tooth – a needle is inserted in the web between thumb and index finger.

For tonsillectomy, a needle is inserted approximately 5 cm (2”) above the wrist.

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Pain Inhibiting Mechanism

It can be -

Endogenous

Exogenous

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Endogenous Method of Controlling Pain Includes -

1) Removing the cause: It is a desirable methods. It is imperative that any removal leave no permanent environmental changes in tissue, since this condition would then be able to create the impulse, even though the original causative factor had been eliminated.

2) Blocking the pathways of painful Impulses

This can be done by injecting drug possessing local analgesic property in proximity to the nerve involved.

Thus preventing those particular fibers from conducting any impulses centrally beyond that point. These two method act by altering pain perception.

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3) Raising the pain threshold :

Raising pain threshold depends on the pharmacological activity of drugs possessing analgesic properties.

These drugs raise pain threshold and therefore alter pain reaction, conceptually there are two components of pain

(a) Nociceptive

(b) Affective component.

The path of nociceptive component is spinothalamic tract Thalamus. This component is purely physical component of pain.

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4) Affective Component

It is the psychological component associated with pain. The path is that some fibers from STT to thalamus terminate in some intermediate stations in the reticular formation of brain stem and are called spinoreticular thalamic system.

Non-narcotic analgesic like aspirin can inhibit the nociceptive but not the affective component of pain whereas opioid (Morphine) inhibit affective as well as nociceptive components of the pain. They act centrally at cortical and sub cortical centers, to change patient mind and his reaction towards pain

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5) Preventing pain reaction by cortical depression

Eliminating pain by cortical depression is by the use of general anesthesia.

6) Using Psychosomatic Method

This method affects both pain perception and pain reaction. It include audio analgesia

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Questions asked-two type

General questions

Specific questions

Diagnosis based on specific questions and tests

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Some general questions are-

What can I do for you?

Pt give response in three ways-

Historical, Diagnostic & Factual

What sort of pain are you having ?

Varied response affected by

Physical, psychological, social factors

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Do you have any reaction to hot cold and sweetness-?

This questions differentiate between the dental pain or pain due to non dental causes & we have to analyze the responses and have to get an impression of the severity of the response.

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Pain to sweetness

Pain to cold

Pain on application of cold but relieved by hot

Delayed response to heat

Unexplained sensitivity to cold in posterior teeth

Root filled teeth sensitive to cold

Pain on biting-vital posterior teeth

Pain on biting-vital anterior teeth

Pain on eating

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Pain relieved by placing hand on the side of the face

Pain on ascent or descent

Pain ass. with exertion or after exertion

Pain on swallowing

Bilateral pain

Pain on waking in the morning

Pain in the afternoon or evening

Pain at a particular time each day

Pain when the Pt goes out in the cold

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SITE OF PAIN

Observation of the manner in which the Pt uses their hands and fingers while describing the pain provide information About the origin of pain

Placing a fingernail between the tooth

Moving a fingernail on the tooth

Holding one tooth

Placing a finger over the apex of the tooth

Pressing over the gingival margin

Holding or moving several teeth

Pressing over the zygoma

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Pressing under the maxilla

Pressing on side of maxilla with rotary movement or pressing on the body of mandible with finger in motion

Using more than one finger for describing the pain

Bilateral pain

Pain on percussion of more than one tooth

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OTHER QUESTIONS ARE

When did the pain start?

Where did the pain start ?

Does any thing relieve the pain?

Have you been able to sleep?

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PULPAL PAIN

It is the most commonly experienced pain in and near the oral cavity.

Pulpal pain can be diagnosed based on clinical signs and symptoms

Histological finding.

Clinically pulp is referred as healthy, reversible pulpitis, irreversible pulpitis.

Histological as acute, chronic & hyperplastic.

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HYPEREMIAThe increased pressure against the sensory nerve endings in the pulp might

well produce the sensation of pain. Application of cold produce a sharp hypersensitive response and heat produce true transient hyperemia and a dull pain.

An assessment of pain intensity at the time of stimulation, dental history& a thorough dental examination allow the clinician to differentiate among the normal pulp, dentin hypersensitivity, and the reversible inflamed pulp.

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Hyperactive pulpalgia :- It is characterized by a short, sharp, shock pain is felt as a sensation of sudden shock. It is never spontaneous.

Dentin Hypersensitivity :- Pain arise in response to thermal, chemical, tactile or osmotic stimuli and is not caused by any other dental defect or pathology. This pain is explained by, hydrodynamic theory postulated by Brannstrom.

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Characteristic features of irreversible pulp condition are :Hyperalgesia in the initial stage

Dull throbbing ache in the later stage

Lingering pain on application of stimuli

Pain is spontaneous

Cause referred pain in other areas

Relief is provided by cold

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Acute Pulpalgia :- Pain is nagging or boring pain which may at first be localized but finally becomes diffuse or referred to another area in mild pulpalgia but in advanced lesion, pain is excruciating and relieved by cold.

Chronic Pulpalgia :- Mild pain that is quite diffuse and is difficult to locate source of pain. It is likely to cause referred pain which is also mild.

Hyperactive pulpitis :- Pain or slight discomfort from food coming against the tooth or on taking extreme of hot & cold.

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Internal desorption :

Pain is mild and at tolerable level and closely resemble chronic pulpalgia.

Incomplete fracture or split tooth :

Pain range from those of constant unexplained hyper sensitive pulp to constant unexplained toothache. The most frequent complaint is that of a tooth painful to bite on, with occasional mild ache.

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PERIODONTAL PAINLocalized, deep throbbing pain

Involving inflammation of PDL around one or more teeth

Mobility

Localized bleeding

Presence of pocket

In radiograph loss of bone is there

Pain last for hour or day

Involve tooth is tender on percussion

If pain involve multiple teeth including opposing teeth then occlusal trauma should considered

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Periradicular pain

Acute apical periodontitis

The pain has been described as constant, gnawing, throbbing and pounding. Tooth is tender and slightly elevated in its socket. The pain is most persistent, lasting 24 hours a day.

Acute apical abscess

Pain is similar to AAP but somewhat lower in intensity. Involved tooth is painful to movement or mastication

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Chronic apical periodontitis :

It is seldom painful.

Chronic apical abcess/suppurative apical periodontitis :

It is generally symptoms free. When draining fistula is closed, discomfort ensue.

Periodontal lesion pain :

Acute gingival or periodontal abscess

Tooth is painful to bite on and is not so deep seated or throbbing as that of apical abscess.

Pain is spontaneous

Associated localized swelling is there

Presence of deep PDL pocket is there.

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Pericoronitis :-

Severe radiating pain in posterior mouth region and inability to comfortably close or open mandible.

Tissue distal to erupting molar is most painful to touch.

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EAR PAINOdontogenic infection of posterior teeth may refer pain to the ear/TMJ area.

Similarly middle ear infection/otitis media/mastoiditis may be confused with odontogenic pain. In otitis media pain is acute, severe, throbbing and exacerbate on lowering the head. Pain may be referred to tooth, TMJ, tonsils, tongue, throat, trachea and thyroid.

It is unlikely for the middle ear infection/otitis media/mastoiditis pain to be exclusively expressed as jaw pain.

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SINUS & PARANASAL PAIN

In acute maxillary sinusitis pain may be stabbing, with severe aching pressure. Pain is frequently referred upward under the orbit and downward over the maxillary posterior teeth. Pain is referred in all the teeth in the quadrant and exacerbated when head is placed below the knee

In chronic sinusitis there is dull constant pain. The location of these symptoms may vary from the maxilla and maxillary teeth in maxillary sinusitis, to the upper orbit and frontal process in frontal sinusitis and at the junction of the hard and soft palate, occipital and mastoid process in sphenoid sinusitis.

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TEMPOROMANDIBULAR JOINT ARTICULAR DISORDERS

Capsulitis and Synovitis

Chief complaint is continuous pain over the joint aggravated by function. Swelling may be evident and patient may complaint of acute malocclusion, restricted mouth opening and teeth pain.

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Internal Derangement : It includes meniscus displacement, formation of intra articular adhesion and

various forms of arthritis.

There occur limited jaw opening, deviation on opening, joint clicking, crepitus and pain directly localized to the joint area in front of the tragus of the ear.

The pain is dull, boring ache but may be more acute when exacerbated by wide mouth opening. The symptoms become progressively worse and the degree of pain increase.

TMJ pain is often referred into temple, cheek and posterior dental area of the maxilla and mandible.

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It results from an abnormality in one or more components of the nervous system i.e. peripheral, central or autonomous. They are characterized as :-

Do not require presence of noxious stimuli in contrast to somatic pain which does.

Pain manifestation are usually maintained by neuroplasticity that is change in nervous pathway carrying pain.

When neuroplasticity is prolonged it result in a state of chronic or pathophysiologic pain.

NEUROPATHIC PAIN

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Hyper excitability of IInd order neuron i.e. central sensitization

Allodynia

Hyperalgesia

Pain is bright, stimulating and burning

Pain that is relatively unresponsive to low doses of narcotic analgesic

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Neuralgias

Trigeminal Neuralgia

Etiology:

Precise cause is unknown. Evidence indicates it may be due to vascular compression of gasserian ganglion, viral infection of neuron or nerve sheath may be there.

It primarily involves either maxillary or the mandibular division but sometimes it may involve ophthalmic division. Pain is severe and lancinating, shooting into the bone and teeth.

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Electric like quality of pain is unique and is rarely encountered in odontogenic infections.

The pain episode last only second at a time. Although paroxysms may occur in rapid succession.

A trigger zone exists somewhere on the facial skin or occasionally in the oral cavity.

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Treatment:

It is essential to establish diagnosis and avoid any invasive procedure.

Carbamazipine (Tegretol)

Peripheral neurectomy

Rhizotomy

Alcohol injection

Cryotherapy

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Radiofrequency lesioning

Laser therapy

Surgical decompression

Trans cutaneous ganglionic neurolysis

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Post herpetic Neuralgia This disease represent a recrudescence of a latent virus located in sensory

ganglion. The painful lesions of shingles cause a deep, boring ache involving not only the superficial mucosal and cutaneous tissues but also the maxillary and mandibular bones. Occurrence of prodromal pain obscure the diagnosis.

Prodromal pain is acute and electric like and the pain associated with vesicular eruption is deep and boring. Once the vesicles clear, the residual pain is of burning quality and chronic. The quality of pain may be confused with odontogenic pain but the history of vesicular eruption is sufficient to make a diagnosis

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Treatment of post herpetic neuralgia:

TENS

Anti seizure drugs

Analgesics

Topical preparation

Refer to neurologist

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Glosso Pharyngeal Neuralgia :

It include unilateral rarely bilateral stabbing pain in the lateral posterior pharyngeal and tonsilar area, the base of the tongue, down in to the throat, the Eustachian tube or ear and down the neck. Sometimes the pain radiates into vagus region and may be associated with salivation, flushing, sweating, tinnitus, cardiac arrhythmias, hypertension, vertigo or syncope.

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Eagle’s Syndrome :

It is similar to those of gloss pharyngeal neuralgia but involve compression of the area of IXth nerve by a calcified elongation of styloid process of the temporal bone.

Precipitating factors include fast rotation of head, swallowing, pharyngeal motion from talking and chewing.

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Vasogenic craniofacial pain

In general pain is deep, throbbing, pulsing or pounding quality, occasionally sharp and with an aching and burning background.

Migraine

Classic migraine headache begin as ache but usually develops in to pain of a throbbing, pulsating or bating nature. One episode can last for several hrs to a day.

Somatosensory areas are most common field and consist of dysesthesias that start in one hand and spread up to involve the ipsilateral side of the face, nose and mouth. The headache itself is predominantly unilateral in the frontal, temporal, or retro bulbar areas, although it may occur in the face or in a single tooth.

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Cluster headache (Sphenopalatine neuralgia)

It can be classified as:

CLASSIC and CHRONIC TYPE

CLASSIC type affect patient mostly in spring season.

CHRONIC type occurs through out the year.

It is often mistaken for acute pulpitis of maxillary posterior teeth.

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CLUSTER HEADACHE

It has temporal pattern. Tend to occur in “Clusters” a series of one to eight 20-180 minute attack/day lasting for several week or months.

The pain is a severe, unilateral, continuous intense ache or burning that often occur at night.

The most common sites are either around and behind the eye radiating to the forehead and temple, infraorbitaly into maxilla and occasionally into the teeth and rarely to the lower jaw and neck.

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Treatment

Use of oxygen at the time of attack relieves pain and used for diagnosis of pain.

Ergotamine tartarate may cause vasoconstriction and contraindicated in hypertensive patient.

CCBs like Nifedipine prevents pain paroxysms.

Corticosteroids alleviating pain and preventing pain occurrence.

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MYOFACIAL PAINThe most common form of musculoskeletal pain affecting the head,

neck and face.

The main characteristic features are ->

Myofacial trigger point

Muscle affected have a reduced active range of movement

Referred pain in reproducible patterns remote from the site of the rigger point.

A jump sing and verbal response or reflex reaction occur on palpation of the trigger point

Pain is deep, dull aching and provocable.

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ATYPICAL ODONTALGIA

The most likely mechanism involved in atypical odontalgia (AO) is related to deafferentation following injury to a nerve. Deafferentation refer to the partial or total loss of an afferent nerve supply from a particular area, following trauma during dental procedure. Nerve damage is reversible in most patient but in some patient (3%).

It is permanent. Pain may not appear for week, month or even a year after the procedure. It has been hypothesized that there is genetic predisposition towards pain in these patients.

Involvement of sympathetic nervous system (SMP) in AO has been suggested.

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Characteristics of pain in atypical odontalgia are:

Chronic aching pain

Pt feel it as deep within the bone & it is hard to localize.

In many Pt symptoms appears to wonder from site to site.

Intensity of pain also varies.

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PAIN PATHWAYS AND MEDICATIONS

Pain Pathways Medications

Peripherally (at the nociceptor) Cannabinoids, NSAIDs, Opioids, Tramadol, Vanilloid receptor antagonists (i.e., capsaicin)

Peripherally(along the nociceptive nerve)

Local anaesthetics, Anticonvulsants (except the gabapentinoids)

Centrally(various parts of the brain)

Acetaminophen, Anticonvulsants (except the gabapentinoids), Cannabinoids, Opioids, Tramadol

Descending inhibitory pathwayin the spinal cord

Cannabinoids, Opioids, Tramadol, Tricyclic antidepressants, SNRIs

Dorsal horn of the spinal cord Anticonvulsants, Cannabinoids, Gabapentinoids, NMDA receptorantagonists, Opioids, Tramadol, Tricyclic antidepressants, SNRIs

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CONCLUSION

• Pain is bad, but not feeling pain can be worse.

• Individuals with a congenital absence of pain receptors are extremely rare but not unknown. Such individuals are very poor at avoiding accidental injuries, and often inflict mutilating injuries on themselves.

• As a result, their life span is usually short. thus pain, although unpleasant, is a protective sensation with enormous survival value. 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.

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• Every day patient seeks care for the reduction or elimination of pain.

• Nothing is more satisfying to the clinician than the successful elimination of pain.

• 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. 

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REFRENCES

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1. Bell`s ‘Orofacial pain’, 5th edition, Jeffrey P. Okeson.

2. Text book of Medical Physiology, 2nd edition, Chaudhari.

3. Text book of Medical Physiology, 10th edition, Arther C Gyton.

4. Dental Clinics of North America 1978: 22 (1); 1-61.

5. Text book of ‘Oral medicine’- 10th edition, Burkett’s.

6. Gray's Anatomy – 38th Edition, Churchill Eivingstone.

7. Understanding “Medical physiology”- 3rd edition, R L Bijlani.

8. Core Topics in Pain – Anita Holdcroft, Sian Jagger.

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9. Pain – Wikipedia, the free encyclopedia

10. Rolf-Detlef Treede. Neurophysiological studies of pain pathways in peripheral and central nervous system disorders. J Neurol (2003) 250 : 1152–1161.

11. Ascending Sensory Pathways, Chapter 10.

12. Pain pathway & Medications – Painexplained.ca, The Canadian Pain Society.

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