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.
Neuropathic 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.
Sokal
David M
DM
Queens Medical Centre, School of Biomedical Sciences, E Floor, University of Nottingham, Nottingham NG7 2UH, UK.
Chapman
Victoria
V
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects*; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors
D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D009118:Muscimol; D001640:Bicuculline