Pain Pathways PDF

PAIN "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" Prostaglandins are chemical substances that are believed to increase the sensitivity of pain receptors by enhancing the painprovoking effect of bradykinin Sub...

PAIN "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" Prostaglandins are chemical substances that are believed to increase the sensitivity of pain receptors by enhancing the painprovoking effect of bradykinin Substance P is a chemical found in C fibers and amplifies the pain signal Chemicals that inhibit the transmission or perception of pain, such as endorphins and enkephalins GATE CONTROL THEORY non-painful input closes the nerve "gates" to painful input pain is "gated" or modulated by past experience PHYSIORX TENS nonnociceptive fibers are selectively stimulated with electrodes in order to produce this effect and thereby lessen pain PRESYNAPTIC INHIBITION presynaptic inhibition of the dorsal nerve endings can occur through specific types of GABA receptors CLASSIFICATION Nociceptive transient while noxious stimuli present Chronic (3 months/ 6 months) Benign causes Cancer pain NOCICEPTIVE capacity to detect the presence of potentially damaging stimuli NOCICEPTIVE capacity to detect the presence of potentially damaging stimuli NOCICEPTIVE Somatic deep superficial Visceral VISCERAL Sensitive less so Stretch/ Ischaemia/Inflammation cutting/ burning accompanied by ANV DEEP SOMATIC nociceptors in ligaments, tendons, bones, fasciae and muscles blood vessels, SUPERFICIAL SOMATIC nociceptors in skin & subcutaneous tissue NOCICEPTIVE Peripheral injury/ inflammation REVERSIBLE sensory adaptations ➡︎ PAIN HYPERSENSITIVITY NEUROPATHIC PAIN MAJOR HEALTH PROBLEM INJURED Nervous system persistent neural changes/ ⬆︎sensitivity/ ⬇︎threshold NEUROPATHIC PAIN susceptible persons genetic polymorphisms NEUROPATHIC PAIN Heterogenous/ pathologic neural plasticity differing etiologies/ genetic/ environmental factors NEUROPATHIC PAIN PATHOPHYSIOLOGY Sensory nerve damage direct insult to primary neurons/ peripheral neuropathy cell death/ ⬇︎transduction (terminal atrophy)/ ⬇︎conduction (⬇︎ periph axons) ⬇︎transmission (⬇︎central terminals) NEUROPATHIC P NEGATIVE symptoms POSITIVE symptoms PERIPH NEUROPATHY all sensory/ numbness after traumatic nerve injury specific/ ⬆︎heat threshold/ degeneration intraepithelial C fibres in early peripheral DIABETIC Neuropathy & CHEMORx Neuropathy PERIPHERAL SENSITISATION peripheral terminals to inflammatory mediators ⬇︎ threshold ⬆︎ excitability peripheral neuritis (nerve lesions ± tissue inflammation) allodynia hyperalgesia ROLE TRPV1 non selective cation channel After partial nerve injury, TRPV1 is upregulated in uninjured sensory fibers diabetic neuropathy TRPV1 expression changes leading to development of thermal hyper- and hypoalgesia. TRPV1 ACTIVATORS EXOGENOUS temperature greater than 43 °C (109 °F) acidic conditions; capsaicin TRPV1 ACTIVATORS ENDOGENOUS low pH (acidic conditions), the endocannabinoid anandamide, N-oleyl-dopamine, and N-arachidonoyl-dopamine TRPV SENSITISERS damage inflammation (Prostaglandins/ bradykinin activation PLC) ⬆︎ sensitivity TRPV DESENSITISERS long exposure capsaicin paradoxical analgesic effect capsaicin ECTOPIC ACTIVITY Spontaneous pain after injury paresthesia, dysthesia, pain. CLINICAL target voltage gated Na channels CENTRAL SENSITIZATION AMPLIFIES PAIN REDUCES THRESHOLD CENTRAL SENSITIZATION MECHANISTIC EXPLANATION LOW THRESHOLD A OR C FIBERS CAN BEGIN TO PRODUCE PAIN SPREAD OF SENSITIVITY BEYOND AREAS OF TISSUE INJURY SPREAD OF SENSITIVITY BEYOND DAMAGED NERVE TERRITORY REPEATED STIMULI AT A FIXED INTENSITY CAN LEAD TO A PROGRESSIVE INCREASE IN PAIN PAIN MAY LONG OUTLAST A PERIPHERAL STIMULUS CENTRAL SENSITIZATION PLAYERS SYNAPTIC CHANGES NMDA/ AMPA/ mGluR glutamate / substance P NK1 receptors MAJOR CENTRAL SENSITIZATION MAJOR PLAYERS A𝛃 fibres ⬆︎neuropeptide expression physical changes in spinal circuitry CENTRAL SENSITIZATION LOSS of INHIBITION from the dorsal horn TACTILE ALLODYNIA Inhibiting GABA and glycine in the spinal cord increases A-fiber-mediated excitatory transmission CNS PLASTICITY AFTER NERVE INJURY IMMUNE CONTRIBUTION