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 (200-250g) were anaesthetised with isoflurane (2%) and underwent a midline laparotomy with gentle manipulation of the viscera, and the effects of pre- (30min) or post- (5h) operative treatment with MPEP (1, 3 or 10mgkg(-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 6h post-surgery (44.5+/-2.4% decrease; p<0.01 vs. anaesthesia only controls) and persisted for 48h. Surgery had no effect on thermal withdrawal latency. Both pre-operative and post-operative administration of 10mgkg(-1)MPEP 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.
Dolan
Sharron
S
Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, UK. sharron.dolan@gcal.ac.uk
Nolan
Andrea Mary
AM
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007813:Laparotomy / Q000009:adverse effects*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C121465:6-methyl-2-(phenylethynyl)pyridine