Etiology and Pathophysiology of Various Pain Syndromes

1. Etiology and Pathophysiology of Various Pain Syndromes

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 Adapted with permission from Fields HL, Price DD. In: Harrington A, ed. The Placebo Effect. An InterdisciplinaryExploration. Cambridge, Mass: Harvard University Press; 1997:106.

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 ofPathologic 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. cell Adapted with permission from Fields HL, Price DD. In: Harrington A, ed. The Placebo Effect. An InterdisciplinaryExploration. Cambridge, Mass: Harvard University Press; 1997:108.

22. Mechanisms of Neuropathic Pain • Noninflammatory states • Inflammatory states

23. Pathophysiology of Neuropathic Pain • Ectopic activity in the peripheral pathways, including axons and DRG • CNS mechanisms

24. Radicular and Discogenic Neuropathic Pain Mechanisms • Ectopic activity of the nerve root nervi nervorum • Sensitization and ectopic activity of the nociceptors innervating spinal periosteal structures, ie, annuli and ligaments • Possible role of abnormal nociceptors overgrown within the intradiscal space, postsurgical epidural scars, degenerated facet joints • CNS sensitization and reorganization

25. Neuropathic Pain: Central Mechanisms Peripheral neuropathic events can be complicated by temporary or long-term CNS changes, such as central sensitization and then reorganization of the pain pathways at the dorsal horn level

26. Neuropathic Pain and SMP • Some neuropathic pains are sustained, at least in part, by sympathetic efferent activity • SMP • Expression of alpha-adrenergic receptors on injured C-fibers may be a relevant mechanism of SMP, but others are possible • Clinical findings consistent with CRPS signal an increased likelihood of SMP

27. Nociceptive Pain Neuropathic Pain PNS peripheral nervous system PNS Peripheral sensitization “Healthy” nociceptors Abnormal nociceptors CNS central nervous system CNS Central sensitization Normal transmission Central reorganization Physiologic state Pathologic state Pappagallo M. 2001.

28. Nociceptive Pain • Sensitization and activation of “healthy” nociceptor endings and recruitment of “silent” nociceptors • “Soup” of inflammatory algogenic agents, such as protons, prostaglandins, bradykinin, serotonin, adenosine, histamine, cytokines

29. Low Back Pain and Sciatica: Nociceptive/ Inflammatory Pain Mechanisms • Activation and sensitization of the nerve root nervi nervorum from root compression/traction • Sensitization of the nociceptors of the annulus fibrosus, periosteal spinal structures, and ligaments, due to acute inflammation, eg, status post trauma • Hyperalgesia (deep spinal and dermatomal) due to central sensitization

30. Fibromyalgia Syndrome: Pathophysiology • Central-nervous-system abnormalities • Muscle pathology • Psychopathology • Genetic predisposition

31. Myofascial Pain Syndrome: Pathophysiology • Current pathophysiologic knowledge relies significantly on clinical examination • Histologic studies of trigger points have not been particularly helpful • Local ischemic factors due to prolonged muscle contraction may play a role in the development of the pain • Denervation supersensitivity has been suggested by some to be the cause

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