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

Neurosci Lett. 2003 May 15;342(1-2):85-8. doi: 10.1016/s0304-3940(03)00259-3.

Abstract

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.

MeSH terms

  • Action Potentials
  • Animals
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Lumbosacral Region
  • Neurons / drug effects*
  • Pain / drug therapy
  • Pain / physiopathology*
  • Pyridines / pharmacology*
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / physiology
  • Sciatic Nerve / injuries
  • Spinal Cord / drug effects*
  • Spinal Cord / physiopathology*

Substances

  • Excitatory Amino Acid Antagonists
  • Grm5 protein, rat
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • 6-methyl-2-(phenylethynyl)pyridine