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

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

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

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

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

Mismatch between stimulus and response stimulus הגירוי התגובה response כאב אלחוש hypoalgesia, analgesia

Mismatch between stimulus and response stimulus הגירוי התגובה response כאב sensitisation ריגוש allodynia hyperalgesia

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

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

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

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

tactile allodynia in neuropathy

classical labeled-line model touch pain innocuous noxious DRG AA C 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

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

“central sensitization” “specificity” labeled line WDR “gate control” regulated convergence descending control control by afferent input "A  pain" touch pain touch or painrelativelyineffectivesynapse

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

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

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

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

P+P+ BT +

gracely

"relatively ineffective synapses"  dynamic control of RF

primary sensory neurons

convergence divergence