Background and objectives: Spinal gamma-aminobutyric acid (GABA) receptors have been shown to modulate post-nerve injury-induced allodynia. This study sought to examine the antiallodynic effects of a GABA analog gabapentin [1-(aminomethyl)cyclohexaneacetic acid], given by subarachnoid injection in a rat neuropathic pain model.
Methods: The rats were prepared with lumbar subarachnoid catheters, and allodynia was induced in rats by ligation of the L5-6 nerve roots (Chung model).
Results: Spinal injection of gabapentin resulted in a dose-dependent (10-1,000 microg) antagonism of the allodynia at doses that had no detectable effect on motor function. Subarachnoid injection of either the GABA A antagonist bicuculline (0.3 microg), or the GABA B antagonist CGP 35348 (30 microg) 5 minutes before or 60 minutes after injection of GABA receptor agonist did not reverse the antiallodynic effects produced by gabapentin.
Conclusions: Gabapentin shows antiallodynic effect, but its mechanism is not known. The failure to reverse this effect by GABA A or B antagonists at doses that reverse the effects of the respective agonists suggests that gabapentin is involved in the modulation of spinal systems by mechanisms that do not involve either a GABA A or a GABA B site.