title: Involvement of mGluR(5) on acute nociceptive transmission.
abstract: The effect of the mGluR(5) antagonist, MPEP (2-Methyl-6-(phenylethynyl)-pyridine), and of the mGluR(1) antagonist, AIDA((RS)-1-Aminoindan-1,5-dicarboxylic acid), were examined on nociceptive neurons in the ventroposterolateral (VPL) nucleus of the thalamus in response to pressure stimuli to the contralateral hindpaw of rats under urethane anesthesia. Intravenous (i.v.) injection of MPEP (0.1, 1, and 10 mg/kg) blocked responses to noxious stimulation 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 noxious 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 stimulation. To investigate the site of action of MPEP, intra-thalamic injections were made during electrophysiological recordings. Using this method, the mGluR(5) antagonist did not affect nociceptive responses, suggesting that thalamic receptors were not involved in this action. On the other hand, the NMDA thalamic receptors seem to be involved because the NMDA receptor antagonist, MK801, successfully blocked responses to noxious pressure stimulation following intra-thalamic injections. In the spinal cord in vitro model, MPEP (30 microM, 60 min) was also able to attenuate ventral root potentials after single shock electrical stimulation of the dorsal root and inhibit wind-up response evoked by repetitive stimulation. Taken together, these findings suggest that blockade of the mGluR(5), but not mGluR(1) decreases nociceptive transmission in the thalamus and that these effects may be mediated by spinal cord receptors.
authors.affiliation: Pharmacology Department, GlaxoWellcome Medicine Research Centre, Via Fleming 4, 37100, Verona, Italy. fb23261@glaxowellcome.co.uk
authors.forename: F
authors.initials: F
authors.lastname: Bordi
authors.forename: A
authors.initials: A
authors.lastname: Ugolini
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D020651:Ventral Thalamic Nuclei / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1; C121465:6-methyl-2-(phenylethynyl)pyridine