The interaction between intrathecal neostigmine and GABA receptor agonistsin rats with nerve ligation injury

Nerve ligation injury may produce a pain syndrome that includes tactile all odynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma -aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interac tions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 sp inal nerves and chronic intrathecal catheter implantation. Tactile allodyni a was measured by applying von Frey filaments ipsilateral to the lesioned h indpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 mu g), muscimol (0.1-10 mug), and baclofen (0.1-3.0 mug) were administered to obtain the dose-response curve and the 50% effective dose (ED50). Fractions of ED50 values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The dru g interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal th reshold of the lesioned hindpaw. Both analyses revealed a synergistic inter action for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that t he activation of both muscarinic and GABA, receptors is required for synerg istic interaction.