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Pathophysiology of Pain. NociceptionNociception The detection of tissue damage by specialized transducers connected to A-delta and C-fibers.

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Presentation on theme: "Pathophysiology of Pain. NociceptionNociception The detection of tissue damage by specialized transducers connected to A-delta and C-fibers."— Presentation transcript:

1 Pathophysiology of Pain

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

3 PainPain 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 Proportionate to the stimulation of the nociceptor When acute When acute – Physiologic pain – Serves a protective function – Normal pain Pathologic when chronic Pathologic when chronic

5 Classification of Pain: Neuropathic Pain Sustained by aberrant processes in PNS or CNS Sustained by aberrant processes in PNS or CNS Disproportionate to the stimulation of nociceptor Disproportionate to the stimulation of nociceptor Serves no protective function Serves no protective function Pathologic pain Pathologic pain

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

7 Classification of Pain: Idiopathic Pain No underlying lesion found yet, despite investigation No underlying lesion found yet, despite investigation Pain disproportionate to the degree of clinically discernible tissue injury 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 Midbrain Medulla Spinal Cord Thalamus Pons

10 Pain-Inhibitory and Pain-Facilitatory Mechanisms Within the Dorsal Horn A-DELTA A-BETA C Neuronal circuitry within the dorsal horn. Primary afferent neuron axons synapse onto spinothalamic neurons and onto inhibitory and excitatory neurons. TO BRAIN + + _ + 0 STT NEURON

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 Pain-processing mechanisms function abnormally – Examples: neuropathic pain syndromes Nociception is sustained by chronic injury Nociception is sustained by chronic injury – Example: arthritis

14 Mechanisms of Pathophysiologic Pain: Peripheral Processes Mechanisms of Pathophysiologic Pain: Peripheral Processes Injured or diseased nerve(s) Injured or diseased nerve(s) Growth of axonal sprouts Growth of axonal sprouts Formation of ectopic foci 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 Repeated impulse activity in C nociceptive neurons produces sensitization of STT neurons over time Sensitization of STT neurons leads to 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 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 Enhanced postsynaptic effects by NMDA- receptor sensitization Tonic activity in C nociceptors A-DELTA A-BETA TO BRAIN + + _ + 0 STT NEURON C

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

19 Enhanced postsynaptic effects by NMDA- receptor sensitization Tonic activity in C nociceptors A-DELTA A-BETA TO BRAIN + + _ + 0 STT NEURON Loss of Inhibitory Interneuron Function C

20 Brain-to-Spinal-Cord Modulation of Pain

21 Pain Modulation Mechanisms Brain centers/pathways that descend to the spinal cord and modulate pain Brain centers/pathways that descend to the spinal cord and modulate pain Tail-flick test Tail-flick test Off-cells inhibit transmission of pain- related information to the brain Off-cells inhibit transmission of pain- related information to the brain On-cells facilitate transmission of pain- related signals to the brain On-cells facilitate transmission of pain- related signals to the brain

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

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