The mGluR5 selective antagonist 6-methyl-2-(phenylethynyl)-pyridine reduces the spinal neuron pain-related activity in mononeuropathic rats

in rats with chronic constriction of one sciatic nerve (CCI rats), showing behavioural signs of neuropathic pain, 6-methyl-2(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, was intraperitoneally administered at 0.75, 1.0 and 1.5 mg/kg or spinally microejected and the effects on the lumbar wide dynamic range neurons activity were investigated. In CCI rats MPEP at 1.0 and 1.5 (but not at 0.75) mg/kg, or spinally microejected induced a significant reduction of the spontaneous (SA) and noxious evoked activity (NEA), and a significant decrease of the suppression of the afterdischarge duration. In sham rats SA was unaffected and NEA was significantly reduced by 1.0 and 1.5 mg/kg MPEP dosages. These findings indicate that the metabotropic GluR5 receptor plays a role in the spinal cord processes underlying neuropathic pain and represents a potential target for new therapeutic approaches. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.