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Activation of Sensory Neurons in Arthritic Pain

Amitesh Narayan

“An unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described in terms of such damage” –
The International Association for the Study of Pain

Subjective sensation

carried by C fibers Nociceptive neuron transmits pain to spinal cord via unmyelinated C fibers & myelinated A-delta fibers. throbbing. carried through A-delta axons in skin Slow – aching.5 to 2.Pain Sources Fast vs.0 m/sec. • larger A-delta fibers carry impulses @ rate of 5 to 30 m/sec. • smaller C fibers carry impulses @ rate of 0. Acute vs. burning. Chronic . Slow Pain – Fast – localized.

irritation).characteristics of pain – Aching (impingement). Radiating Referral/Radiation – Referred – site distant to damaged tissue that does not follow the course of a peripheral n. Burning (n.. Radiating – follows peripheral n.Pain Mnemonics Pattern: onset & duration Area: location Intensity: level Nature: description P-Q-R-S-T format Provocation – How the injury occurred & what activities   the pain Quality . Sharp (acute injury). diffuse Severity –Pain scale Timing – When does it occur? .

Pain Transmitting Nerves Afferent (Ascending) –from periphery to the brain First Order neuron Second Order neuron Third Order neuron Efferent (Descending) – transmit impulses from the brain to the periphery .

localized sensation (prickling. unmyelinated • Delayed onset. fast. sharp. stinging.First Order Neurons Stimulated by sensory receptors End in the dorsal horn of the spinal cord Types A-alpha – non-pain impulses A-beta – non-pain impulses • Large. diffuse nagging sensation (aching. thinly myelinated • Short duration. burning) C – pain impulses due to chemicals or mechanical • Small diameter. respond to light touch & lowintensity mechanical info A-delta – pain impulses due to mechanical pressure • Large diameter. bright. myelinated • Low threshold mechanoreceptor. throbbing) .

Substantia Gelatinosa (SG) .Second Order Neurons Receive impulses from the FON in the dorsal horn Lamina II. to CNS. A-delta. & C Nociceptive specific • Receive impulses from A-delta & C Ends in thalamus .determines the input sent to T cells from peripheral nerve • T Cells (transmission cells): transmission cell that connects sensory n. neurons that organize stimulus input & transmit stimulus to the brain Travel along the spinothalamic tract Pass through Reticular Formation Types Wide range specific • Receive impulses from A-beta.

Third Order Neurons Begins in thalamus Ends in specific brain centers (cerebral cortex) Perceive location. intensity Allows to feel pain. integrate past experiences & emotions and determine reaction to stimulus . quality.

Endogenous opioid peptides .Descending Neurons Descending Pain Modulation (Descending Pain Control Mechanism) Transmit impulses from the brain (corticospinal tract in the cortex) to the spinal cord (lamina) Periaquaductal Gray Area (PGA) – release enkephalins Nucleus Raphe Magnus (NRM) – release serotonin * release of these neurotransmitters inhibit ascending neurons. Stimulation of the PGA in the midbrain & NRM in the pons & medulla causes analgesia.endorphins & enkephalins .

substance that causes local vasodilation &  permeability of capillaries * Both are generated by noxious stimuli.transmits pain-producing impulses Acetylcholine – transmits motor nerve impulses Enkephalins – reduces pain perception by bonding to pain receptor sites Norepinephrine – causes vasoconstriction 2 types of chemical neurotransmitters that mediate pain • Endorphins . which activate the inhibition of pain transmission Can be either excitatory or inhibitory .morphine-like neurohormone. thought to  pain threshold by binding to receptor sites • Serotonin .Neurotransmitters Chemical substances that allow impulses to move from one neuron to another Found in synapses Substance P .

Golgi Tendon Organs Nociceptors – painful stimuli mechanosensitive chemosensitive .heat. Merkel’s corpuscles (deep pressure) Thermoreceptors . light or deep pressure Meissner’s corpuscles (light touch). heat. cold Krause’s end bulbs ( temp & touch).Sensory Receptors Mechanoreceptors – touch. tension. (in joint capsules & ligaments – change of position) Proprioceptors – change in length or tension Muscle Spindles. Pacinian corpuscles (deep pressure). Ruffini corpuscles (in the skin) – touch.

37) Nerve endings may: Respond to phasic activity . free n. endings.produce an impulse when stimulus is  or . Krause’s end bulbs) . (muscle spindles.” (Prentice. adapt to a constant stimulus (Meissner’s corpuscles & Pacinian corpuscles) Respond to tonic receptors produce impulses as long as the stimulus is present.Nerve Endings “A nerve ending is the termination of a nerve fiber in a peripheral structure. but not during sustained stimulus. p.

Nerve Endings Merkel’s corpuscles/disks Sensitive to touch & vibration Slow adapting Superficial location Most sensitive Krause’s end bulbs – Thermoreceptor Ruffini corpuscles/endings Thermoreceptor Sensitive to touch & tension Slow adapting Meissner’s corpuscles – Sensitive to light touch & vibrations Rapid adapting Superficial location Free nerve endings Afferent Detects pain. mechanical stimuli Pacinian corpuscles Sensitive to deep pressure & vibrations Rapid adapting Deep subcutaneous tissue location . temperature. touch.

Isolectin B4 (IB4) positive neurons. Calcitonin gene-related peptide (CGRP)-expressing neurons (McCarthy & Lawson 1990).Phenotype classification of primary afferent nerve fibres Classified a/c to their neuropeptide phenotype: a. recognized using selective CGRP antibodies. b. . Large diameter non-nociceptive neurons and nerve fibres that bind the RT97+ve antibody (Bergman et al 1999) which recognizes phosphorylated epitopes on identified neurofilament proteins (Johnstone et al 1997). which are nonpeptidergic nociceptive neurons (Silverman&Kruger 1990). and c. classed as peptidergic nociceptive neurons.

Spinal Cord and CNS Pathways from Pain Receptors .


Antinociceptive systém .

Endorphin Response .

increased sensitivity to further noxious mechanical stimulation (Hyperalgesia).Articular afferents and inflammation Trauma to the joint increased sensitivity to load and movement of the joint within the normal range (allodynia). . brought about by changes in the sensitivity of primary afferent nerve fibres (through spinal processing of joint input and by processing within higher centres).

low threshold group II articular afferents show acute and transient changes in response to joint manipulation which resolve within few hours. Schaible & Schmidt 1988a). BUT show enhanced responses to joint movements. .Articular afferents and inflammation Following joint inflammation. Coggeshall et al 1983. Guilbaud et al 1985. Articular afferents belonging to groups III and IV begin to show ongoing spontaneous activity in the absence of joint movement.

These alterations in the firing characteristics of group III and IV afferents are the result of a marked reduction in the mechanical threshold for activation of articular mechanoreceptors and it contributes.Articular afferents and inflammation Furthermore. in part. many units which were previously Mechano-insensitive develop receptive fields and may also show ongoing spontaneous activity. . to psychophysical measures of allodynia and hyperalgesia experienced in humans.

. Loss of the normal articulating surfaces and abnormal bone pathology results in chronic inflammation that can last years. this is largely due to the destruction of cartilage and bone remodelling (osteophytes or bony spurs). inflammatory response may be protracted due to abnormal pathology in the joint tissues.Articular afferents and inflammation In chronic disease. In OA.

Schmidt RF 1988a Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. Dixon ASJ 1970 Intraarticular pressure in rheumatoid arthritis of the knee. Osteoarthritic Joint Pain: Novartis Foundation Symposium 260. Chadwick and Jamie Goode. Sojka P 1991 Receptors in the knee joint ligaments and their role in the biomechanics of the joint. I. Brain Res 272:185-188. Novartis Foundation 2004. Coggeshall RE. Ann Rheum Dis 261-265. Schmidt RF 1983 Discharge characteristics of fine medial articular afferents at rest and during passive movements of inflamed knee joints. Langford LA. Johansson H. Hong KAP. Jayson MIV. Grubb. ISBN: 0-470-86763-9. Crit Revs Biomed Eng 18:341-368.References Blair D. Schaible H-G. Schaible H-G. Activation of sensory neurons in the arthritic joint. J Neurophysiol 60:2180^2195 . Pressure changes during passive joint distension. Volume 260 Edited by Derek J. Sjolander P.

. Grubb BD 1993 Afferent and spinal mechanisms of joint pain.References Schaible H-G. Pain 55:5-54.