PHYSIOLOGICAL ASPECTS OF PAIN

Definition of painIASP 1979 Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

Definition of terms: Nociception: Neural response to a noxious stimuli. Noxious stimulus: Tissue damaging or potentially damaging stimulus Antinociception: Blockage of nociception

Sensations: Protopathic(noxiuous) Epicritic(nonnoxious).

Classification of Pain According to duration Acute pain and chronic pain According to reaction time Fast pain and Slow pain According to Patho physiology Nociceptive pain and Neuropathic pain According to Etiology Post-operative pain and Cancer pain

4 distinct processTransduction : noxious stimuli causes generation of electrical activity in sensory nerve endings.Transmission: impulse CNS.Modulation Perception

Pain Pathway The sensory information from the somatic segments enters the spinal cord through dorsal roots of spinal nerves.From the spinal cord to the brain, sensory signals are carried through one of the two alternative sensory pathways.1. The dorsal column-medial lemniscal system.2. The antero-lateral system-which transmit sensation of pain, thermal sensation, and crude touch.

Are naked, afferent nerve endings of myelinated A and unmyleinated C fibers that encode the occurrence, intensity duration and location of noxious stimuli.

3 types of pain receptors -Mechanosensitive -Mechanothermal -Polynodal pain receptors

PAIN RECEPTORS

2 types of fibers: small myelinated A 2-5 06-30m/s Sharp, fast, well localized pain.

Unmyelinated C fibers. 0.4-1.2m 0.5-2m/sec Dull, slow, poorly localized.

First order neuronsFirst order neurons send proximal end of their axons into spinal cord via dorsal spinal root at each cervical, thoracic, lumbar and sacral level.

Synapse with second order neurons, interneurons, sympathetic neurons, ventral horn motor neurons.

Pain fibers from head and neck

Trigeminal(V): Gasserian ganglion.Facial(VII): Geniculate ganglion.Glossopharyngeal(IX): Superior petrosal.Vagal(X): Jugular ganglion, ganglion nodosum.

Proximal axonal processes of first order neurons in these ganglia reach the brain stem via respective cranial nerves, where they synapse with second order neurons.

Second order neuronsSegregate according to size, with large myelinated fibers becoming medial, small unmyelinated fibers becoming lateral.Pain fibers may ascend or descend 1-3 segments before synapse.Spinal cord grey matter divided into 10 lamina by Rexed.First 6 lamina make up the dorsal horn, receive all afferent neural activity, principal site of modulation.

Either nociceptive specific or wide dynamic range(WDR).Nociceptive specific serve only noxious stimulus. Arranged in lamina I, normally silent respond to high threshold noxious stimulus.WDR neurons receive non noxious stimuli and from A, A, C fibers. Arranged in mainly in lamina V.

Lamina

LaminaPredominant function InputNameISomatic nociception thermoreceptionA, CMarginal layerIISomatic nociception thermoreceptionC, ASubstantia gelatinosaIIISomatic mechanoreceptionA, ANucleus propriusIVMechanoreceptionA, ANucleus propriusVVisceral & somatic nociceptionA, ANucleus propriusVIMechanoreception ANucleus propriusVIISympathetic Intermediolateral coloumVIIIAMotor hornIXMotor AMotor hornXACentral canal

Spinothalamic tract Main pain pathway.Anterolateral in white matter of spinal cord.Divided into lateral & medial tractLateral tract projects to ventral posterolateral nucleus of thalamus, mediates intensity location & duration of pain. Medial tract projects to medial thalamus, mediates autonomic & unpleasant emotional perception.Some fibers may also project to the reticular activating system.

Alternative pain pathwaysSpinoreticular tract: Mediates arousal & autonomic response to pain.Spinohypothalamic & Spinotelencephalic tract: Activates hypothalamus & evokes emotional behaviour.Spinomesencephalic tract: Activates antinociceptive descending pathway.Spinocervical tract: relays fibers to contra lateral thalamus.

Third order neuronsLocated in the thalamus.Send fibers to the somatosensory areas I & II in post central gyrus of the parietal cortex & superior wall of sylvian fissure.Perception & localization of pain.Fibers from lateral thalamic nuclei project the primary somatosensory cortex.Fibers from intralaminar & medial nuclei project to anterior cingulate gyrus.

Physiology of nociceptionNociceptors: high threshold for activation. Delayed adaptation, sensitization & afterdischarges. Two types of ion channels VR1, VRL-1. Both responds to high temperature, bradykinin, histamine, serotonin, H+, K, prostaglandins, ATP .

Visceral PainMechanism underlying visceral pain include peritoneal inflammation, visceral distension and exaggerated smooth muscle contraction.

Smooth muscle contraction is increased by adrenergic sympathetic and cholinergic parasympathetic innervations.

Chemical mediators of painSeveral neuropeptide & excitatory amino acids function as neurotransmitters.Important are substance P, calcitonin, glutamate.Substance P a 11 amino acid peptide is synthesized by first order neurons both peripherally & in dorsal horn.

Neurotransmitter Receptor Effect Substance PNK 1Excitatory CalcitoninExcitatoryGlutamate NMDA, AMPAExcitatoryAspartate NMDA, AMPAExcitatoryATPP1, P 2ExcitatorySomatostatin Inhibitory AcetylcholineMuscarinicInhibitory Encephalins ,,.Inhibitory NorepinephrineSerotonin 25-HTInhibitory Inhibitory GABAA, BInhibitory

Modulation of painMay occur at nociceptor, spinal cord or in supraspinal structures, can either inhibit or facilitate pain.

Peripheral modulation

Central modulation

Peripheral modulationSensitization of nociceptors by potassium ion and ATP released by tissue trauma and cell destruction.

Neuropeptides and amino acids (substance P, Bradykinin, Histamine) trigger inflammation response and sensitize nociceptors and cause hyperalgesia.

Spread of hyperalgesia away from the site by antidromal propogation of signals along peripheral branches of sensory nerve and release of substance P vasodilatation release of neuropeptides and amino acids in the surrounding tissue.

Central modulationRepetitive afferent activation of A delta and C fibers leads to altered characteristics in spinal cord dorsal horn neurons.

Changes sensitization, wind up, expansion of receptive field and enhancement of spinal reflexes.

Mechanism:- release of excitatory neurotransmitters from nerve terminals .

THEORIES OF PAIN PERIRHERAL PATTERN THEORY

CENTRAL SUMMATION THEORY

SENSORY INTERACTION THEORY

GATE CONTROL THEORY

PERIRHERAL PATTERN THEORYSinclair & Weddell.1950.All fiber endings are alike.Pattern of pain is produced by intense stimulation of nonspecific receptors.

CENTRAL SUMMATION THEORYLivingstone.1943.Intense stimulation resulting from nerve & tissue damage activates fibers that project in the spinal cord which in turn projects to brain that underlie pain mechanism.

SENSORY INTERACTION THEORYNoordenbos.1959.Large fibers inhibits & small fibers excite central transmission neurons.

GATE CONTROL THEORYMelzack & Wall.1965, 1968, 1978.The term Gate control is now applied to rapidly acting mechanisms which accepts and control the passage of impulses from the afferent fiber input to cells which may then trigger the various effector systems & evoke sensation.Stimulation of large myelinated fibers produced a negative dorsal root potential, stimulation of C fibers caused a positive dorsal root potential.

They postulated that these potentials, which were a reflection of presynaptic inhibition or excitation, modulated the activity of secondary transmitting neurons(T cells) in the dorsal horns, & that this modulation was mediated through an inhibitory interneuron(I cells) placed the T cell in laminaV of the dorsal horn & the still unidentified cells in laminae II & III.

The essence of this theory is the large diameter fibers excite the I cells, which in turn causes a presynaptic inhibition of T cells. Conversly the small small afferent fibers inhibits the I cells leaving the T cells in an excitatory state.

Impulses from the dorsal horn must also be under the control of a descending system of fibers from brain stem, thalamus .

Systemic responses to acute painCardiovascular effects.Respiratory effectsGastrointestinal and urinary effects.Endocrine effectsHaematological effects

CARDIOVASCULARStimulation of sympathetic neurons and subsequent tachycardia, increased stroke volume, cardiac work and myocardial oxygen consumption.

Risk of deep vein thrombosis

Respiratory Reduced Vital capacity and Forced expiratory volume.

Decrease of diaphragmatic function

Reduced pulmonary compliance, muscle splinting and inability to breathe deeply or cough forcefully leading to hypoxia, hypercarbia, retention of secretions, atelectasis, and pneumonia .

Gastrointestinal and urinary: Ileus, nausea, vomiting, hypo motility of the urethra and bladder.

Neuroendocrine and metabolic: catecholamine and catabolic hormone secretion (cortisol, adrenocorticotrophic hormone(ACTH), antidiuretic hormone, growth hormone, cyclic adenosine monophosphate (CAMP), glucagon, aldosterone, renin, angiotensin 2

References

For all the happiness mankind can gain is not in pleasure but in rest from pain. John Dryden