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.
Sotgiu
Maria Luisa
ML
Istituto di Bioimmagini e Fisiologia Molecolare, CNR, Via Fratelli Cervi 93, 20090 (Mi), Segrate, Italy. maria.luisa.sotgiu@ibfm.cnr.it
Bellomi
Paola
P
Biella
Gabriele E M
GE
D000200:Action Potentials; D000818:Animals; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008161:Lumbosacral Region; D009474:Neurons / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine