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 metabotropic glutamate receptor (mGluR) compound, (S)-4-carboxyphenylglycine ((S)-4CPG), or the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilipine maleate (MK-801), on mechanical allodynia and cold hyperalgesia associated with chronic constriction injury (CCI) of the sciatic nerve in rats. Also, the effects of early (twice-daily injections on days 0-3) or late (twice-daily injections on days 8-11) (S)-4CPG treatment on the injury-related mechanical allodynia and cold hyperalgesia 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 treatment significantly attenuated the development of mechanical allodynia (90 and 270 nmol) and cold hyperalgesia (270 nmol). However, late treatment with (S)-4CPG did not reduce the nociceptive behaviours in either behavioural task. These data not only confirm that the NMDA receptor plays a role in chronic nociception, but also suggest that Group I mGluRs are more critically involved in the development, and not the maintenance, of mechanical allodynia and cold hyperalgesia associated with CCI in rats. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.