Electrophysiologic evidence for increased endogenous GABAergic but not glycinergic inhibitory tone in the rat spinal nerve ligation model of neuropathy

Background: Changes in the inhibitory activity mediated by gamma -aminobuty ric acid (GABA) and glycine, acting at spinal GABA(A) receptors and strychn ine-sensitive glycine receptors, are of interest in the development of neur opathic pain. There is anatomic evidence for changes in these transmitter s ystems after nerve injuries, and blocking either GABA(A) or glycine recepto rs has been shown to produce allodynia-like behavior in awake normal animal s. Methods: In this study, the possible changes in GABAergic and glycinergic i nhibitory activity in the spinal nerve Ligation model of neuropathic pain m ere studied by comparing the effects of the GABA(A)-receptor antagonist bic uculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. Results: Bicuculline produced a dose-related facilitation of the A delta -f iber-evoked activity in all study groups and increased C-fiber-mediated act ivity in the spinal nerve ligation group but not in either of the control g roups. There were no differences in the effect of bicuculline on low thresh old responses between the study groups. The glycine receptor antagonist str ychnine did not have a statistically significant effect on any of the param eters studied in any of the control groups. Conclusions: These results support the idea of an increased GABAergic inhib itory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after nerve injury.