Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates hyperalgesia and allodynia associated with sciatic nerve constriction injury in rats

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Abstract
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.