THE CONTRIBUTION OF METABOTROPIC GLUTAMATE RECEPTORS (MGLURS) TO FORMALIN-INDUCED NOCICEPTION

The present study examined the role of mGluRs in nociceptive responses of male Long-Evans rats following a subcutaneous (s.c.) injection of 1% (30 mu l) or 2.5% (50 mu l) formalin to the plantar surface of the hindpaw. Intrathecal (i.t.) administration of the mGluR4/mGluR6-mGluR8 agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), the mGluR1/mGl uR5 antagonists, (S)-4-carboxyphenylglycine ((S)-4CPG) or (S)-4-carbox y-3-hydroxyphenylglycine ((S)-4C3HPG), but not the non-selective antag onist, (+)-a-methyl-4-carboxyphenylglycine ((+)-MCPG), to the lumbar s pinal cord slightly reduced second phase nociceptive responses. An i.t . injection of the mGluR1/mGluR5 agonist, (RS)-3,5-dihydroxyphenylglyc ine ((RS)-DHPG) or the mGlu2/mGluR3 agonist, (1S,3S)-1-aminocyclopenta ne-1,3-dicarboxylic acid ((1S,3S)-ACPD), but not 'R,2'R,3'R)-2-(2'3'-d icarboxy-cyclopropyl)-glycine (DCG-IV), dose-dependently enhanced form alin-induced nociception in the second phase. In addition, the facilit ation of nociceptive responses induced by (1S,3S)-ACPD or (RS)-DHPG wa s reduced by prior i.t, administration of the mGluR antagonists, (+)-M CPG or (S)-4C3HPG, respectively, as well as by the N-Methyl-D-aspartat e (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid ( D-AP5). These results indicate that although mGluRs may play a minor r ole in formalin-induced nociception, mGluR agonist-related facilitatio n of formalin scores may reflect an interaction with the NMDA receptor .