Role of central and peripheral mGluR5 receptors in post-operative pain in rats

Pain. 2005 Mar;114(1-2):195-202. doi: 10.1016/j.pain.2004.12.016. Epub 2005 Jan 21.


Metabotropic glutamate receptors (mGluRs) have previously been shown to play a role in pain transmission during inflammatory or neuropathic pain states. However, the role of mGluR5 in post-operative pain remains to be fully investigated. The present study was conducted to characterize analgesic activity of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in the skin-incision-induced post-operative pain model in rats. MPEP is a potent and selective mGluR5 antagonist with high affinity (K(i)=6.3+/-0.9 nM) in rat cortex using [(3)H]-MPEP as a radioligand, while not competing with the mGluR1-selective radioligand [(3)H]-R214127 (K(i)>10,000 nM) in rat cerebellum. Post-operative pain was examined 2 h following surgery using weight-bearing (WB) difference between injured and uninjured paws as a measure of non-evoked pain. In this model, MPEP, as morphine, showed dose-dependent effects and full efficacy after systemic administration (ED(50)=15 mg/kg, i.p. for MPEP, ED(50)=1.3 mg/kg, s.c. for morphine). In addition, intrathecal (i.t.) and intracerebroventricular (i.c.v.) MPEP reduced WB difference (ED(50)=65 microg/rat i.t. and ED(50)=200 microg/rat i.c.v.). Interestingly, intraplantar ( injection of MPEP either before or after surgery induced a similar reduction in WB difference (ED(50)=90 microg/rat, while contralateral MPEP injection did not produce any effect. These results demonstrate that both peripheral and central mGluR5 receptors play a role in nociceptive transmission observed during post-operative pain. In addition, the data suggest that mGluR5 antagonists could offer a new therapeutic approach to the treatment of post-operative pain.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / pharmacology
  • Morphine / therapeutic use
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Pyridines / metabolism
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*


  • Grm5 protein, rat
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Morphine
  • 6-methyl-2-(phenylethynyl)pyridine