Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids.
The contribution of C-fiber neuropeptides and excitatory amino acids (EAAs) as central mediators of secondary hyperalgesia was assessed by examining the effects of intrathecal (i.t.) administration of receptor-selective agonists and antagonists on foot-withdrawal latencies (from 48 degrees C water), both before and after heat injury of the contralateral hindpaw. The hyperalgesia which develops in the hindpaw contralateral to a heat injury, could be reproduced in uninjured rats following i.t. injection of substance P, neurokinin A and N-methyl-D-aspartate (NMDA) but not following calcitonin gene related peptide (CGRP), neurokinin B, kainate or (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). Contralateral hyperalgesia was reversed by the substance P antagonist Arg1,D-Pro2,D-Phe2-D-His9-substance P, and the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (APV), but not by the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When the limb of the injured hindpaw was pretreated with the C-fiber neurotoxin capsaicin, hyperalgesia in the contralateral hindpaw was unaffected. Furthermore, prior to injury, the capsaicin pretreatment itself produced hyperalgesia in the contralateral hindpaw. The results give support for a contribution of both C-fiber neuropeptides and EAAs to central nervous system plasticity and secondary hyperalgesia following heat injury.
Coderre
T J
TJ
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Que., Canada.
Melzack
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D007839:Functional Laterality; D006358:Hot Temperature; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D012018:Reflex; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D009479:Neuropeptides; D011810:Quinoxalines; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002211:Capsaicin; D007608:Kainic Acid