Morphine‐induced depression of spinal excitation is not altered following acute disruption of GABAA or GABAB receptor activity

Abstract Loss of spinal inhibitory mechanisms is thought to contribute to the pathophysiology of abnormal pain states, including neuropathic pain. By using an evoked spinal field potential technique, the hypothesis was tested here that decreased spinal GABAergic control underlies poor response to morphine (MOR) that often accompanies neuropathic pain. Therefore, field potentials evoked by electrical peripheral nerve stimulation during spinal superfusion with MOR were recorded in rats rendered neuropathic by a spinal nerve ligation (SNL) procedure, and compared to responses recorded in nai¨ve rats. MOR effects on evoked field potentials were then assessed in rats in which spinal GABAergic inhibition had been acutely reduced by treatment with GABA A and GABA B receptor-antagonists. In nai¨ve animals, field potentials evoked by peripheral C fibre-input were significantly decreased by spinal superfusion with 1 μM MOR, whereas those elicited by Aδ fibre input were reduced to a lesser extent also (10 μM, p 50 value (2.17 ± 0.38 μM) for MOR was found in rats subjected to SNL, relative to nai¨ve rats (8.65 ± 0.76 μM). In contrast, MOR failed to reduce field potentials evoked by peripheral Aδ fibre-activation at any dose tested (up to 1 mM). C fibre- and Aδ fibre-evoked spinal field potentials disinhibited by prior application of the GABA B or GABA A receptor-antagonists CGP35348 (1 mM) or bicuculline (50 μM), respectively, were both significantly reduced by MOR, with IC 50 values not significantly differing from those in nai¨ve animals. Two-way analysis of variance revealed no interaction of MOR with either CGP354348 ( p  = 0.42) or BIC ( p  = 0.14). Evidence is presented here that injury to the primary afferent system results in significant changes in the ability of spinal MOR to depress field potentials evoked by peripheral input. However, the present findings do not support a pathogenic role for decreased GABAergic inhibition in such changes.