Neurophysiology of pain

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outlineIntroduction and definitionTypes of painPain receptorsChemical mediators of painDual nature of painTheories of pain perceptionPhysiology of dental painPain assessment scales

REFERENCESFrederick A. Curro PAIN DCNA 1978;22(1):1-173

GUYTON . Textbook of Medical Physiology. 11th edition : Pg no. 588-606

JOHN I .INGLE: Endodontics. 5THed: Pg No. 287-299

A .DRAY British journal of anesthesia 1995;75:125-131

Indian J Physiol Pharmacol NEUROPHYSIOLOGY OF PAIN : INSIGHT TO OROFACIAL PAIN O. P. TANDON, V. MALHOTRA, S. TANDON AND I. DSILVA 2003;47 (3):247269 Carl L von Baeyer, PhD RDPsych Childrens self-reports of pain intensity: Scale selection, limitations and interpretation.

Pain is perfect misery, the worst of evils; and excessive, overturns all patience.

John Milton, Paradise Lost

Pain is not a simple sensation but rather a complex neurobehavioral event involving at least two components.

First is an individuals discernment or perception of the stimulation of specialized nerve endings designed to transmit information concerning potential or actual tissue damage (nociception).

Second is the individuals reaction to this perceived sensation (pain behaviour).

Pain is difficult to define, quantify, and understand is reflected in the numerous ways in which it has been described

Dorlands Medical Dictionary defines pain as a more or less localized sensation of discomfort, distress, or agony resulting from the stimulation of specialized nerve endings.

Definition of painInternational Association for the Study of Pain (IASP) An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Pain is always subjective.

Each individual learns the application of the word through experiences related to injury in early life.

It is unquestionably a sensation in a part of the body, but it is also always unpleasant and therefore also an emotional experience.

Psychological reasons for pain perception.

Difficult to make distinction based on subjective report.

Accept as pain even if only a psychological basis.

Many people report pain in the absence of tissue damage or any likely pathophysiological cause, usually this happens for psychological reasons. There is no way to distinguish their experience from that due to tissue damage, if we take the subjective report. If they regard their experience as a pain and if they report it in the same way as pain caused by tissue damage, it should be accepted as pain.


Types of pain (Acc. to Guyton) FAST PAIN


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

Slow pain also goes by many names, such as slow burning pain, aching pain,throbbing pain, nauseous pain, and chronic pain.

generally elicited by chemical types of stimuli

Not felt in deeper tissues

Fast pain is also described by many alternative names, such as sharp pain, pricking pain, acute pain, and electric pain.

generally elicited by mechanical & thermal types of stimuli.

Pain receptorsThe pain receptors in the skin and other tissues are all free nerve endings.The receptors which mediate pain are called NOCICEPTORS.

small unmyelinated C fibres or myelinated A afferent neurons.

widespread in the superficial layers of the skin as well as in certain internal tissues, such as the periosteum, the arterial walls, the joint surfaces, and the falx and tentorium in the cranial vault.


Components of a typical cutaneous nerve

Types of Stimuli Excite Pain ReceptorsPain can be elicited by multiple types of stimuli. They are classified as mechanical, thermal, and chemical pain stimuli.

fast pain is elicited by the mechanical and thermal types of stimuli

slow pain can be elicited by all three types.

Mechanical stimulation due to:Excessive pressure or tension on nerves. E.g.- a blow on the head, pulling of hair etc.Compression of nerves by tumour.

Thermal stimulation- Raising skin temperature above 45C or exposure to cold (0C) is painful.

Chemical stimulation by irritant chemicals such as histamine, kinins & prostaglandins released from damaged tissue.

Chemical pain mediators

Nociceptors sensitized byNociceptors activated by BradykininHistamineSerotoninIncreased potassium concentrationProteolytic enzymes AcidsAcetlycholine ProstaglandinsSubstance PInterleukins Leukotrienes

Chemical mediatorrs A variety of chemical mediators are able to alter the function of peripheral afferent fibres.

Afferent fibre may be unresponsive even to intense stimuli, but are highly responsive when stimuli induced by inflammation mediators.

Some chemicals may induce influence on function of afferent fibres.

Sensory fibres metabolism and activity is greatly altered by a variety of mediators produced by tissue injury, inflammation.

Substances produced by damaged tissue, afferent fibres, immune cells.

Some mediators like protons, 5-hydroxytryptamine can act directly on membrane ion channel protein to change permeability and cell excitability.

Chemical mediators of pain

Sensory neuron takes information Send information to motor neuron Tissue damage will lead to release of chemicals like potassium ions, histamine etc. conduction of these signals in special nerve fibres A and C fibre Signals head to spinal cord and to brain through spinothalmic pain pathway

Spinothalmic pain fibres runs up to the spinal cord though medulla, Pons, midbrain upto thalamus. Sensory nerves in spinal cord are grouped together in dorsal root ganglion. Signals sent from thalamus upward to primary sensory cortex.

An area in spinal cord called dorsal horn conduct nervous impulses to the brain and back down to spinal cord to area of injury.

Brain does not pass message of removing hand from spike, dorsal horn of the spinal cord sent it to muscle of hand to withdraw quickly.

Further thalamus send signal to areas controlling blood pressure, heart rate, breathing and emotions.

One chemical that seems to be more painful than others is bradykinin.

Increase in potassium ion concentration and proteolytic enzymes that directly attack the nerve endings and excite pain by making the nerve membranes more permeable to ions.

Variety of substance released during tissue damage to cells these have a profound effect on the afferent fibres.

Damaged tissue or blood cells release the polypeptide bradykinin (BK), potassium, histamine, serotonin, and arachidonic acid.

Arachidonic acid is processed by two different enzyme systems to produce prostaglandins and leukotrienes, which, along with BK, act as inflammatory mediators .

Bradykinin acts synergistically with these other chemicals to increase plasma extravasation and produce edema.

Plasma extravasation, in turn, replenishes the supply of inflammatory chemical mediators.

Tissue ischemia as a cause of pain

When blood flow to a tissue is blocked, tissue becomes painful within minutes.

Accumulation of large amounts of lactic acid in the tissue as a consequence of anaerobic metabolism.

It is also probable that other chemical agents, such as bradykinin and proteolytic enzymes, are formed in the tissues.

Muscle spasm as a cause of pain

Partially from the direct effect of muscle spasm in stimulating mechano sensitive pain receptors

Also result from the indirect effect of muscle spasm to compress the blood vessels and cause ischemia

Dual Nature of Pain

Pain has two components:

Pain perception

Pain reaction

Objective component of pain. Emotional experience to the perceived injury.

Physio-anatomic processImpulse is generated after application of adequate stimulus and is transmitted to the CNS. Psycho physiological process and involves the cortex, hypothalamus & thalamus.

This aspect of pain is almost similar in all healthy individuals and varies little from day to dayVaries from individual to individual and also from day to day in the same person.


SENSORY THRESHOLD- defined as the lowest level of stimuli that will cause any sensation-the summation of large sensory fibers from receptors for touch, temperature & vibration.

PAIN THRESHOLD As the stimulus is increased, the sensation becomes stronger until pain is perceived. This is pain threshold.

Fairly constant among individuals.


If the intensity of the stimulus is increased above pain threshold, a level of pain will be reached that the subject can no longer endure. This is pain tolerance or the response threshold.

At this point the individual makes an attempt to withdraw from the stimulus.

Range between the pain threshold and the response threshold is termed as a persons tolerance to pain.

FiberDiameter ()Conduction velocity (m/s)Function


A- beta


A- gamma