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Pathophysiology of Pain

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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Pathophysiology of Pain

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  1. Pathophysiology of Pain

  2. Nociception The detection of tissue damage by specialized transducers connected to A-delta and C-fibers

  3. Pain An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage, or both

  4. Classification of Pain Nociception • Proportionate to the stimulation of the nociceptor • When acute • Physiologic pain • Serves a protective function • Normal pain • Pathologic when chronic

  5. 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

  6. Classification of Pain: Mixed Pain • Nociceptive components • Neuropathic components • Examples • Failed low-back-surgery syndrome • Complex regional pain syndrome

  7. Classification of Pain: Idiopathic Pain • No underlying lesion found yet, despite investigation • Pain disproportionate to the degree of clinically discernible tissue injury

  8. Normal Central Pain Mechanisms

  9. Peripheral and Central Pathways for Pain Ascending Tracts Descending Tracts Cortex Thalamus Midbrain Pons Medulla Spinal Cord

  10. 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

  11. 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.

  12. Mechanisms of Pathologic Pain

  13. Mechanisms of Pathologic Pain: General Considerations • Pain-processing mechanisms function abnormally • Examples: neuropathic pain syndromes • Nociception is sustained by chronic injury • Example: arthritis

  14.  Mechanisms of Pathophysiologic Pain: Peripheral Processes •  Injured or diseased nerve(s) • Growth of axonal sprouts • Formation of ectopic foci

  15. 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

  16. 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.

  17. 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

  18. Intracellular Mechanisms of Sensitization Reproduced with permission from Mao J, et al. Pain. 1995;61:361.

  19. 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

  20. Brain-to-Spinal-Cord Modulation of Pain

  21. 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

  22. Pathophysiology of Pain: Conclusion • Neuronal plasticity • Nociceptor, spinal cord, brain • Pain-facilitatory and pathophysiologic mechanisms • Wind-up phenomenon • Central sensitization • Modulating mechanisms • Ascending • Descending

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