Effects of Intrathecally Injected Glutamate and Substance P Antagonists on Repeated Cold Stress-Induced Hyperalgesia in Rats

Abstract

To determine the role of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examined the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-azabicyclo [2.2.2]octan-3-amine (CP-96, 345, 0.3—3 nmol/rat), the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV, 1—10 nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 1—10 nmol/rat) suppressed RCS-induced hyperalgesia in a dose-dependent manner, without affecting the nociceptive threshold of normal rats. Combinations of any two of CP-96, 345 (3 nmol/rat), APV (10 nmol/rat), and CNQX (10 nmol/rat) did not produce a larger inhibition than that produced by their single doses. The present results suggest that the enhancement of the substance P-NK-1 receptor system and glutamate-NMDA and non-NMDA receptor systems in the spinal dorsal horn is at least partly involved in the RCS-induced hyperalgesia. © 1995, The Pharmaceutical Society of Japan. All rights reserved.