Parenterally administered kainic acid induces a persistent hyperalgesia inthe mouse and rat

Nociceptive primary afferent C-fibers express a subset of glutamate recepto rs that are sensitive to kainic acid. Thus, we tested the possibility that activation of these receptors alters nociception. Intraperitoneal (i.p.) in jection of kainic acid induced a persistent thermal hyperalgesia, when test ed using the hot plate (mice) and tail flick (mice and rats) assays, and me chanical hyperalgesia when tested using von Frey monofilaments (rats), but had no effect on acetic acid-induced chemical nociception (mice). When admi nistered i.p., 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an (R,S)-alpha- amino-3-hydroxy-5-methylisoxazole-4-proprionic acid HBr/kainate (AMPA/KA) a ntagonist, completely blocked hyperalgesia. When injected intrathecally (i. t.), kainic acid itself failed to induce hyperalgesia and AMPA/KA antagonis ts given i.t. also failed to attenuate the hyperalgesic effect of kainic ac id administered i.p., indicating that the spinal cord is not the primary si te of action. Kainic acid injected subcutaneously in the back of mice decre ased response latencies in the hot plate and tail flick assays, indicating that hyperalgesia is achieved by a variety of parenteral routes of injectio n. Histological evaluation of rat spinal cord and dorsal root ganglia revea led no neurodegenerative changes 24 h after kainic acid. Together these dat a suggest that a persistent hyperalgesia results from the transient activat ion of AMPA/KA receptors that are located outside the spinal cord, perhaps on the distal projections of primary afferent fibers. (C) 1999 Internationa l Association for the Study of Pain. Published by Elsevier Science B.V.