Antinociceptive effects following intrathecal pretreatment with selective metabotropic glutamate receptor compounds in a rat model of neuropathic pain.
In the present study, we examined the effects of intrathecal pretreatment (twice daily injections on postoperative (PO) days 0-3 with the selective Group I (mGluR1a) mGluR antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid ((RS)-AIDA), the selective Group I (mGluR5a) antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), the selective Group II mGluR agonist, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC) or the selective Group III mGluR agonist, L-2-amino-4-phosphonobutyrate (L-AP4), on mechanical and cold hypersensitivity associated with chronic constriction injury (CCI) of the sciatic nerve in rats. Mechanical and cold sensitivity was assessed prior to surgery (baseline) and then at 4, 8 and 12 days following CCI. Pretreatment with all of the mGluR agents produced reductions in the development of mechanical hypersensitivity. In addition, all the mGluR agents, except MPEP, were effective in reducing the development of cold hypersensitivity. This study demonstrates that spinal Group I mGluR antagonism, and Group II or III mGluR agonism, can effectively decrease the development of mechanical and cold hypersensitivity associated with CCI in rats. In addition, the results can be interpreted to suggest that activation of spinal Group I mGluRs contributes to spinal plasticity leading to the development of neuropathic pain, and that this effect is offset by activation of groups II and III mGluRs.
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Montreal, Canada.
Kim
K
Fisher
Celeste
C
Lefebvre
Terence J
TJ
Coderre
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003251:Constriction, Pathologic / Q000150:complications / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors*
C095756:1-aminoindan-1,5-dicarboxylic acid; D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate