INTRATHECAL ADMINISTRATION OF THE MGLUR COMPOUND, (S)-4CPG, ATTENUATES HYPERALGESIA AND ALLODYNIA ASSOCIATED WITH SCIATIC-NERVE CONSTRICTION INJURY IN RATS

The present study examined the effects of intrathecal (i.t.) treatment (twice-daily injections on post-operative (PO) days 0-8) with the met abotropic glutamate receptor (mGluR) compound, (S)-4-carboxyphenylglyc ine ((S)-4CPG), or the non-competitive N-methyl-D-aspartate (NMDA) ant agonist, dizocilipine maleate (MK-801), on mechanical allodynia and co ld hyperalgesia associated with chronic constriction injury (CCI) of t he sciatic nerve in rats. Also, the effects of early (twice-daily inje ctions on days 0-3) or late (twice-daily injections on days 8-11) (S)- 4CPG treatment on the injury-related mechanical allodynia and cold hyp eralgesia were assessed in CCI rats. Results demonstrated that 8-day ( S)-4CPG or MK-801 treatment attenuated mechanical allodynia (up to PO days 12 or 16, respectively) and cold hyperalgesia (up to PO days 8 or 16, respectively). Results also demonstrated that early (S)-4CPG trea tment significantly attenuated the development of mechanical allodynia (90 and 270 nmol) and cold hyperalgesia (270 nmol). However, late tre atment with (S)-4CPG did not reduce the nociceptive behaviours in eith er behavioural task. These data not only confirm that the NMDA recepto r plays a role in chronic nociception, but also suggest that Group I m GluRs are more critically involved in the development, and not the mai ntenance, of mechanical allodynia and cold hyperalgesia associated wit h CCI in rats. (C) 1998 International Association for the Study of Pai n. Published by Elsevier Science B.V.