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Pathophysiology of Pain. Nociception. The detection of tissue damage by specialized transducers connected to A-delta and C-fibers. Pain. An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage, or both.
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Nociception The detection of tissue damage by specialized transducers connected to A-delta and C-fibers
Pain An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage, or both
Classification of Pain Nociception • Proportionate to the stimulation of the nociceptor • When acute • Physiologic pain • Serves a protective function • Normal pain • Pathologic when chronic
Classification of Pain:Neuropathic Pain • Sustained by aberrant processes in PNS or CNS • Disproportionate to the stimulation of nociceptor • Serves no protective function • Pathologic pain
Classification of Pain: Mixed Pain • Nociceptive components • Neuropathic components • Examples • Failed low-back-surgery syndrome • Complex regional pain syndrome
Classification of Pain: Idiopathic Pain • No underlying lesion found yet, despite investigation • Pain disproportionate to the degree of clinically discernible tissue injury
Peripheral and Central Pathways for Pain Ascending Tracts Descending Tracts Cortex Thalamus Midbrain Pons Medulla Spinal Cord
Pain-Inhibitory and Pain-Facilitatory Mechanisms Within the Dorsal Horn 0 C A-DELTA A-BETA _ _ + Neuronal circuitry within the dorsal horn. Primary afferent neuron axons synapse onto spinothalamic neurons and onto inhibitory and excitatory neurons. STTNEURON + + + TO BRAIN
Rating of First and Second Pain Intensity Adapted with permission from Cooper BY, et al. Pain. 1986;24:103 and from Lee KH, et al. In: Fields HL, Dubner R, Cervero F, eds. Proceedings of the Fourth World Congress on Pain. New York, NY: Raven Press; 1985:204.
Mechanisms of Pathologic Pain: General Considerations • Pain-processing mechanisms function abnormally • Examples: neuropathic pain syndromes • Nociception is sustained by chronic injury • Example: arthritis
Mechanisms of Pathophysiologic Pain: Peripheral Processes • Injured or diseased nerve(s) • Growth of axonal sprouts • Formation of ectopic foci
Mechanisms of Pathophysiologic Pain: Central Sensitization Processes • Repeated impulse activity in C nociceptive neurons produces sensitization of STT neurons over time • Sensitization of STT neurons leads to • Increased spontaneous impulse activity • Enhanced responses to impulses in nociceptive and non-nociceptive primary afferents • Causes hyperalgesia, allodynia, and spontaneous pain
Temporal summation of second pain (second pain summation is a result of repeated input from C-fiber). Temporal summation of responses of a dorsal horn (STT) neuron to repeated C-fiber stimulation and the effects of the NMDA-receptor antagonist ketamine. Reproduced with permission from Price DD, et al. In: Fields HL, Liebeskind JC, eds. Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues. Seattle, Wash: IASP Press; 1994:66.
Mechanism of Central Sensitization Associated With Tonic C Nociceptor Input 0 A-DELTA C A-BETA Tonic activity in C nociceptors _ _ + + STTNEURON + + + Enhanced postsynaptic effects by NMDA-receptor sensitization + + + + TO BRAIN
Intracellular Mechanisms of Sensitization Reproduced with permission from Mao J, et al. Pain. 1995;61:361.
Loss of Inhibitory Interneuron Function 0 C A-DELTA A-BETA Tonic activity in C nociceptors _ _ + STTNEURON + + + Enhanced postsynaptic effects by NMDA-receptor sensitization + + + + TO BRAIN
Pain Modulation Mechanisms • Brain centers/pathways that descend to the spinal cord and modulate pain • “Tail-flick test” • “Off-cells” inhibit transmission of pain-related information to the brain • “On-cells” facilitate transmission of pain-related signals to the brain
Pathophysiology of Pain: Conclusion • Neuronal plasticity • Nociceptor, spinal cord, brain • Pain-facilitatory and pathophysiologic mechanisms • Wind-up phenomenon • Central sensitization • Modulating mechanisms • Ascending • Descending