Involvement of mGluR(5) on acute nociceptive transmission

The effect of the mGluR(5) antagonist, MPEP (2-Methyl-6-(phenylethynyl)-pyr idine), and of the mGluR(1) antagonist, AIDA((RS)-1-Aminoindan-1,5-dicarbox ylic acid), were examined on nociceptive neurons in the ventroposterolatera l (VPL) nucleus of the thalamus in response to pressure stimuli to the cont ralateral hindpaw of rats under urethane anesthesia. Intravenous (i.v.) inj ection of MPEP (0.1, 1, and 10 mg/kg) blocked responses to noxious stimulat ion in a dose-dependent and reversible manner. AIDA (3 and 15 mg/kg, i.v.), in contrast, had no effect on these cells. MPEP action was selective to no xious stimulation because even when tested at the highest dose (10 mg/kg, i .v.) it did not alter the responses of non-nociceptive neurons to brush sti mulation. To investigate the site of action of MPEP, intra-thalamic injecti ons were made during electrophysiological recordings. Using this method, th e mGluR(5) antagonist did not affect nociceptive responses, suggesting that thalamic receptors were not involved in this action. On the other hand, th e NMDA thalamic receptors seem to be involved because the NMDA receptor ant agonist, MK801, successfully blocked responses to noxious pressure stimulat ion following intra-thalamic injections. In the spinal cord in vitro model, MPEP (30 mu M, 60 min) was also able to attenuate ventral root potentials after single shock electrical stimulation of the dorsal root and inhibit wi nd-up response evoked by repetitive stimulation. Taken together, these find ings suggest that blockade of the mGluR(5), but not mGluR(1) decreases noci ceptive transmission in the thalamus and that these effects may be mediated by spinal cord receptors. (C) 2000 Elsevier Science B.V. All rights reserv ed.