• David M Sokal and Victoria Chapman.
• Queens Medical Centre, School of Biomedical Sciences, E Floor, University of Nottingham, Nottingham NG7 2UH, UK.
• Brain Res. 2003 Feb 7; 962 (1-2): 213-20.

AbstractNeuropathic pain is a common clinical problem with complex aetiology, mechanisms and symptoms. Alterations in spinal gamma-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 microg/50 microl) on electrically-evoked responses of spinal neurones in control, spinal nerve ligated and sham operated halothane-anaesthetised rats were studied. Spinal muscimol significantly (10 microg/50 microl) reduced evoked Abeta-, Adelta- 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 Adelta- and C-fibre evoked neuronal responses compared to Abeta-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 microg/50 microl) were blocked by pre-application of spinal bicuculline (10 microg/50 microl). Following either sham surgery, or spinal nerve ligation, spinal muscimol inhibited Abeta-, Adelta- 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 Abeta- and Adelta-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.

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