INTRATHECAL BACLOFEN AND MUSCIMOL, BUT NOT MIDAZOLAM, ARE ANTINOCICEPTIVE USING THE RAT-FORMALIN MODEL

Both gamma-aminobutyric acid (GABA)(A) and GABA(B) receptor subtypes h ave been implicated in spinally mediated antinociception in acute pain models. In the current study, the formalin test was used as a model o f protracted nociception to examine the effect of intrathecally (i.t.) administered baclofen (GABA(B) agonist), muscimol (GABA(A) agonist) o r midazolam (a benzodiazepine) on antinociception. At doses that did n ot affect motor function, baclofen (0.3 and 1.0 mu g, i.t.) decreased the flinch response in a dose-dependent manner during Phase 1 and Phas e 2. This effect was reversible by the GABA(B)-specific antagonist, CG P35348 {[P-(3-aminopropyl)-P-diethoxymethylphosphinic acid]}. Muscimol (0.3 and 1.0 mu g i.t.) evoked a dose-dependent, bicuculline-reversib le decrease in flinching during Phase 1 and Phase 2, but midazolam had no effect on either phase. No attenuation of the quiescent period bet ween Phase 1 and Phase 2 was seen upon administration of baclofen, mus cimol or midazolam. Additionally, no increase in nocifensive behavior was observed upon administration of either GABA(A) or GABA(B) antagoni sts alone. Therefore, our conclusions are that both GABA(A) and GABA(B ) agonists are antinociceptive at the spinal cord level and that endog enous spinal GABA levels are insufficient for a GABA potentiator to ac t alone in an antinociceptive manner.