BEHAVIORAL AND ELECTROPHYSIOLOGICAL EVIDENCE SUPPORTING A ROLE FOR GROUP-I METABOTROPIC GLUTAMATE RECEPTORS IN THE MEDIATION OF NOCICEPTIVEINPUTS TO THE RAT SPINAL-CORD

A combined study of behavioural and electrophysiological tests was car ried out in order to assess the role of metabotropic glutamate recepto rs (mGluRs) in mediating sensory inputs to the spinal cord of the rat. In the behavioural study the responses of conscious animals, with or without carrageenan-induced inflammation, to noxious mechanical and th ermal stimuli were observed both before and after the intrathecal admi nistration of mGluR antagonists L(+)-2-amino-3-phosphonopropionic acid (L-AP3) and (S)-4-carboxy-3-hydroxyphenylglycine (CHPG). It was found that the mGluR antagonist (S)-CHPG was capable of increasing both mec hanical threshold and thermal latency in both groups of animals, and L -AP3 did so in those with inflammation induced in their hindpaw. Follo wing this study, the responses of single lamina III-V dorsal horn neur ons to an innocuous A beta fibre brush stimulus and a noxious C fibre (mustard oil) stimulus were extracellularly recorded and the effect of ionophoretically applied drugs was examined. Cyclothiazide (CTZ), a s elective antagonist at mGluR(1), markedly reduced the activity evoked by mustard oil, but not that elicited by brushing of the receptive fie ld. Activity induced in dorsal horn neurons by ionophoresing various m GluR subgroup agonists was examined. CTZ successfully inhibited the ac tivity evoked by group I mGluR agonist 3,5-dihydroxyphenylglycine (DHP G). In comparison to the neurons which responded to the ionophoresis o f DHPG, less were activated by the selective mGlu(5) agonist trans-aze tidine dicarboxylic acid (t-ADA). Together these results indicate that group I mGlu receptors, in particular mGluR(1), play a crucial role i n mediating nociception, particularly following a sustained noxious in put. (C) 1997 Elsevier Science B.V.