Modulation of neuropathic pain behavior in rats by spinal disinhibition and NMDA receptor blockade of injury discharge.
When a peripheral nerve is severed, damaged sensory fibers emit a barrage of impulses that lasts for many seconds, or even several minutes ('injury discharge'). We have shown in rats that local anesthetic blockade of this discharge suppresses autotomy (a behavioral model of neuropathic pain). Correspondingly, mimicking prolonged injury discharge with electrical stimulation, especially of C-fibers, increased autotomy. These data support the hypothesis that injury discharge plays a role in the triggering of neuropathic pain. The mechanism of triggering autotomy was investigated using intrathecal injection of agents affecting glutamatergic transmission. A single intrathecal injection at the lumbar enlargement of the NMDA receptor blockers MK-801 and 5-APV, just prior to neurectomy, significantly suppressed autotomy. Blocking glycinergic inhibition just prior to neurectomy with a single strychnine injection strikingly enhanced autotomy. Strychnine enhancement of autotomy was prevented by prior injection of MK-801 or 5-APV. These results suggest that the expression of autotomy in rats, and by inference neuropathic pain in humans, is affected by injury discharge, possibly mediated by long-lasting, NMDA receptor-related, spinal disinhibition.
Department of Physiology, Faculty of Dental Medicine, Hebrew University of Jerusalem, JerusalemIsrael Department of Anesthesiology, Hadassah University Hospital, JerusalemIsrael Department of Anesthesiology, Hasharon Hospital, Petah-TiqvaIsrael.
Ze'ev
Z
Seltzer
Sergiu
S
Cohn
Ruth
R
Ginzburg
BenZion
B
Beilin
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D005998:Glycine / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000523:psychology*; D059348:Peripheral Nerve Injuries; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000502:physiology*; D013331:Strychnine / Q000008:administration & dosage / Q000494:pharmacology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D013331:Strychnine; D005998:Glycine