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.