EFFECTS OF INTRATHECALLY INJECTED GLUTAMATE AND SUBSTANCE-P ANTAGONISTS ON REPEATED COLD STRESS-INDUCED HYPERALGESIA IN RATS

To determine the role of NK-1 substance P receptors and N-methyl-D-asp artate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal ho rn in the hyperalgesia induced by repeated cold stress (RCS), we exami ned the effects of intrathecal injections of antagonists to NK-1, MMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for p aw-pressure stimulation. Intrathecal injections of the NK-1 antagonist xyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3-3 nmol/rat), the MMDA 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 inhibi tion than that produced by their single doses. The present results sug gest 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.