Effects of spinal administration of muscimol on C- and A-fibre evoked neuronal responses of spinal dorsal horn neurones in control and nerve injured rats

Abstract

Neuropathic pain is a common clinical problem with complex aetiology, mechanisms and symptoms. Alterations in spinal γ-aminobutyric acid (GABA) receptors may contribute to persistent pain states. The aim of the present study is to investigate potential changes of spinal GABA A-receptor function following peripheral nerve injury. Effects of spinal administration of the GABA A-receptor agonist muscimol (0.1–30 μg/50 μl) on electrically-evoked responses of spinal neurones in control, spinal nerve ligated and sham operated halothane-anaesthetised rats were studied. Spinal muscimol significantly (10 μg/50 μl) reduced evoked Aβ-, Aδ- and C-fibre responses of spinal neurones in control rats (58±22% of control, P<0.05; 3±2% of control, P<0.001; and 8±7% of control, P<0.001; respectively). Muscimol produced significantly greater inhibition of Aδ- and C-fibre evoked neuronal responses compared to Aβ-fibre evoked neuronal responses in control rats ( P<0.001). C-fibre mediated post-discharge responses and the non-potentiated C-fibre evoked responses were significantly inhibited by muscimol in control rats. Inhibitory effects of muscimol (10 μg/50 μl) were blocked by pre-application of spinal bicuculline (10 μg/50 μl). Following either sham surgery, or spinal nerve ligation, spinal muscimol inhibited Aβ-, Aδ- and C-fibre evoked responses of spinal neurones to a similar extent, however significant inhibitory effects on the post-discharge response were not observed in nerve injured rats. Our data demonstrate that GABA A-receptor control of Aβ- and Aδ-fibre evoked responses are not altered in nerve injured or sham operated rats, compared to control. However, following nerve injury we report a reduction in GABA A-receptor control of C-fibre responses, in particular in relation to post-discharge responses.