EFFECTS OF INTRATHECAL STRYCHNINE AND BICUCULLINE ON NERVE COMPRESSION-INDUCED THERMAL HYPERALGESIA AND SELECTIVE ANTAGONISM BY MK-801

We studied the effects of intrathecally administered strychnine (STR; glycine antagonist; 10 or 30 mug) and bicuculline (BIC; GABA(A) antagonist 1 or 3 mug) on the thermal hyperalgesia which occurs following sciatic nerve constriction injury in rats. Following unilateral application of loose ligatures around the sciatic nerve, all rats typically displayed an ipsilateral thermal hyperalgesia on day 7. Intrathecal STR or BIC administered just after the nerve lesion and on days 1 and 2 after the nerve lesion significantly enhanced in a dose-dependent fashion the magnitude of the thermal hyperalgesia normally observed on day 7, as compared to intrathecal saline (for STR: 30 mug > 10 muj greater-than-or-equal-to saline; for BIC: 30 mug > 10 mug greater-than-or-equal-to saline, p < 0.05). Intrathecal MK-801, an N-methyl-D-aspartate antagonist, was without effect upon the response latency of the normal or sham operated paw, but selectively reversed the hyperalgesia. These results suggest that the loss of a spinal STR- and BIC-sensitive inhibition augments development of the hyperalgesia induced by chronic nerve compression.