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

摘要

To determine the role of NK-1 substance P receptors and /V-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examin-ed the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nocicep-tive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (25,35)-cis-2-(diphenylmethyl)-A'-[(2-methoxyphenyl)-inethyl]-l-azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3—3 nmol/rat), the NMDA antagonist 2-amino-S-phosphonovaleric acid (APV, 1—lOnmol/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.