GABA mechanisms and antinociception in mice with ligated sciatic nerve

In the present study, the effects of GABA (gamma -aminobutyric acid) recept or agonists and antagonists on hyperalgesia induced by sciatic nerve ligati on was investigated in mice. The response to morphine or GABA receptor agon ists was examined 14 days after unilateral nerve ligation by hot-plate test . Intraperitoneal injection of different doses of morphine (3, 6 and 9 mg/k g), 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 respons e of morphine but not that of muscimol or baclofen, in nerve-ligated mice w as significantly less than that induced in the intact animals. The response s induced by muscimol or baclofen in nerve-ligated animals, were reduced by bicuculline or CGP35348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic aci d], respectively. However, morphine in combination with muscimol (2 mg/kg) tends to induce higher response; the combination of the GABA receptor agoni sts with morphine did not show potentiation, but additive effect. The opioi d receptor antagonist naloxone reduced the response induced by muscimol in nerve-ligated animals. It was concluded that although ligation of the sciat ic nerve clearly reduced the analgesic effect of morphine and not that of t he GABA agonists, the results nevertheless indicated that morphine and the GABAA agonist shared the same mechanism of action.