ELECTROPHYSIOLOGICAL STUDIES ON THE SPINAL ROLES OF ENDOGENOUS OPIOIDS IN CARRAGEENAN INFLAMMATION

This electrophysiological study uses the mixed peptidase inhibitor kel atorphan and the selective kappa-antagonist nor-binaltorphimine (nor-B NI) to investigate whether there is altered modulation of spinal nocic eptive transmission by endogenous opioids 3 h after injection of carra geenan into the ipsilateral paw.Intrathecal kelatorphan (5-250 mu g) i nhibited the C-fibre evoked response of dorsal horn neurones in both n ormal and carrageenan animals, with no difference in this inhibitory e ffect found between the 2 groups of animals. In both groups of animals , this inhibition reached a plateau at 50%. Thus there was no change i n the effects exerted by the spinal enkephalins at this point in the i nflammatory state. Nor-BNI (10 and 100 mu g) produced a bidirectional change in the C-fibre evoked response of dorsal horn neurones in both normal and carrageenan animals, facilitating the evoked response of so me neurones whilst inhibiting others. The magnitude of the change in t he neuronal response induced by nor-BNI in carrageenan animals was sig nificantly greater than that seen in normal animals, suggesting a grea ter release of spinal dynorphin in the inflammatory state. Dorsal horn neurones showed a bidirectional change in response as carrageenan-ind uced inflammation developed, although the direction of this change did not correlate with the subsequent direction of effect of nor-BNI. The re was, however, a significant correlation between the magnitude of th e change in the C-fibre evoked response after the injection of carrage enan and the magnitude of change produced in the same cells by nor-BNI . This suggests that there is a strong link between the dynorphin syst em in the spinal cord and the system responsible for producing the cha nges in neuronal response seen post-carrageenan, possibly the N-methyl -D-aspartate (NMDA) receptor system.