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

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.