Effect of metabotropic glutamate receptor subtype 5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine on mechanosensory afferents innervating rat hind paw following inflammation

We investigated whether the metabotropic glutamate receptor subtype 5 (mGluR5) selective antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has direct effects on primary afferent fiber responses to noxious mechanical stimulation following inflammation. Mechanosensory primary afferent fibers innervating the hind paw were recorded in naïve and complete Freunds adjuvant (CFA) inflamed rats. Following intraplantar injection of CFA, afferent fibers showed property changes including expanded receptive fields, burst firing with fast adaptive mechanical responses and a higher incidence of cold and/or heat sensitivities compared to naïve rats. In eight afferent fibers tested following i.v. administration of MPEP, seven fibers showed significantly reduced responses to noxious mechanical stimulation. At a cumulative dose of 10 mg/kg, MPEP inhibited afferent responses to 32.66 ± 11.48% of control. The mean ID50 value of MPEP was 6.49 ± 0.43 mg/kg. In contrast to its inhibitory action in the CFA model, i.v. administration of MPEP produced only a mild reduction of mechanical responses in 3 fibers out of 11 in naïve rats. These results provide direct functional evidence that blockade of peripheral mGluR5 receptors inhibits nociceptive transmission and support previous studies demonstrating a peripheral site of action associated with the antinociceptive effect of MPEP following inflammation.