Blockade of metabotropic glutamate receptor 5 activation inhibits mechanical hypersensitivity following abdominal surgery

Sharron Dolan, Andrea M. Nolan

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This study used the metabotropic glutamate 5 (mGlu5) receptor subtype-selective antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) to characterise the contribution of mGlu5 receptor activity to pain and hypersensitivity in an animal model of post-surgical pain. Adult female Wistar rats (200–250 g) were anaesthetised with isoflurane (2%) and underwent a midline laparotomy with gentle manipulation of the viscera, and the effects of pre- (30 min) or post- (5 h) operative treatment with MPEP (1, 3 or 10 mg kg-1; i.p.) or drug-vehicle on hindpaw withdrawal latency (in seconds) to thermal stimulation (Hargreave’s Test) and response threshold (in grams) to mechanical stimulation (using a dynamic plantar aesthesiometer) were measured. Animals that underwent surgery displayed significant hypersensitivity to mechanical stimulation of the hindpaws. Hypersensitivity was maximum at 6 h post-surgery (44.5 ± 2.4% decrease; p <0.01 vs. anaesthesia only controls) and persisted for 48 h. Surgery had no effect on thermal withdrawal latency. Both pre-operative and post-operative administration of 10 mg kg-1MPEP blocked mechanical hypersensitivity induced by surgery (p <0.01 vs. vehicle treatment). MPEP had no effect on acute nociceptive thresholds in naïve animals. These data suggest that activity at mGlu5 receptors contributes to development of pain and hypersensitivity following surgery.

Original languageEnglish
JournalEuropean Journal of Pain
Publication statusPublished - 1 Aug 2007



  • metabotropic glutamate receptor 5
  • post-surgical pain
  • MPEP
  • hyperalgesia

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