GABA mechanisms and antinociception in mice with ligated sciatic nerve.

Abstract

In the present study, the effects of GABA (gamma-aminobutyric acid) receptor agonists and antagonists on hyperalgesia induced by sciatic nerve ligation was investigated in mice. The response to morphine or GABA receptor agonists was examined 14 days after unilateral nerve ligation by hot-plate test. Intraperitoneal injection of different doses of morphine (3, 6 and 9 mg/kg), muscimol (0.5, 1 and 2 mg/kg) or baclofen (1, 2.5 and 5 mg/kg) induced a dose-related antinociception in both intact and ligated mice. The response of morphine but not that of muscimol or baclofen, in nerve-ligated mice was significantly less than that induced in the intact animals. The responses induced by muscimol or baclofen in nerve-ligated animals, were reduced by bicuculline or CGP35348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid], respectively. However, morphine in combination with muscimol (2 mg/kg) tends to induce higher response; the combination of the GABA receptor agonists with morphine did not show potentiation, but additive effect. The opioid receptor antagonist naloxone reduced the response induced by muscimol in nerve-ligated animals. It was concluded that although ligation of the sciatic nerve clearly reduced the analgesic effect of morphine and not that of the GABA agonists, the results nevertheless indicated that morphine and the GABA(A) agonist shared the same mechanism of action.