Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids.

Article date: 1991/9/30

PubMed ID: 1686478

Journal name: Neuroscience letters (ISSN: 0304-3940)


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.

Author List: Coderre T J, Melzack R

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Amino Acids; Neuropeptides; Quinoxalines; Ibotenic Acid; N-Methylaspartate; 6-Cyano-7-nitroquinoxaline-2,3-dione; 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Capsaicin; Kainic Acid;

Mesh terms: 2-Amino-5-phosphonovalerate/pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids/pharmacology; Animals; Capsaicin/pharmacology; Functional Laterality; Hot Temperature; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; N-Methylaspartate/pharmacology; Neuronal Plasticity/drug effects; Neuropeptides/pharmacology; Pain/physiopathology; Quinoxalines/pharmacology; Rats; Reflex; Time Factors; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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