Somatosensory System and Pain

1. 08-9 פיסיולוגיה מורחב Somatosensory System and Pain lecture 5: Spinal signal processing Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew University of Jerusalem

2. pain pain threshold סף הכאב response touch detection threshold pain threshold stimulus stimulus

3. touch pain * * classical labeled-line model Aδ+C A DRG innocuous noxious

4. some SG neurons are "nociceptive specific" WDR multireceptive Rexed’s laminae X

5. touch pain * * classical labeled-line model Aδ+C A DRG innocuous noxious

6. אלחוש hypoalgesia, analgesia כאב Mismatch between stimulus and response התגובהresponse stimulus הגירוי

7. sensitisation ריגוש כאב hyperalgesia allodynia Mismatch between stimulus and response התגובהresponse stimulus הגירוי

8. inflammation דלקת • burn • infection • abrasion allodynia + hyperalesia • Inflammatory • “triple response” • rubor (red) • calor (hot) • tumor (swollen) • dolor (pain)

9. touch pain * * tactile allodynia is a challenge to the… classical labeled-line model Aδ+C A peripheral sensitization DRG innocuous noxious

10. דלקת sensitization of nociceptors "peripheral sensitization" ריגוש של קולטנים נוסיספטיביים

11. “inflammatory soup” Inflammatory mediators מקדמי דלקת bradykinin histamine prostaglandins 5HT pH (protons) leukotrienes SP, CGRP  “quadruple response”

12. tactile allodynia in neuropathy

13. touch pain C A DRG innocuous noxious • Tactile allodynia is not due to receptor • sensitization • rapid response latency • heat, but no tactile sensitization • tactile allodynia gone with A nerve block • A nerve stimulation  pain • no flare classical labeled-line model

14. optional Torebjork et al. 1992 • Tactile allodynia is A pain • response latency • A nerve stimulation  pain • “secondary hyperalgesia” • ischemic block • mechanosensitization of C-noceptors ? • peripheral neurography (human) • intraneuralmicrostimulation (human) high low electrical threshold

15. descending control relatively ineffective synapse WDR control by afferent input “gate control” regulated convergence "A pain" “central sensitization” touch pain touch or pain “specificity” labeled line

16. Some proposed mechanisms of • central sensitization • activation of NMDA-type glutamate receptors • activation of spinal glia (microglia and astrocytes) • which, in turn, release excitatory molecules (cytokines) • loss of GABAergic interneurons • background spontaneous drive  minor depolarization • sprouting of A afferents into Rexed lamina I • increased intrinsic excitability of spinal WDR neurons

17. WDR LTP, NMDA-R “gate control” regulated convergence “central sensitization”

18. presynaptic inhibition “Gate-control theory” Melzack & Wall 1965

19. פיסיולוגיה מורחב Somatosensory System and Pain lecture 5: Spinal signal processing Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew University of Jerusalem

20. P+ BT+

21. gracely

22. "relatively ineffective synapses" dynamic control of RF

23. primary sensory neurons

24. divergence convergence