GABA-mediated inhibition in rostral ventromedial medulla: role in nociceptive modulation in the lightly anesthetized rat

Local microinjection of GABA_A receptor agonists and antagonists was used to characterize the role of GABA-mediated inhibitory processes in the nociceptive modulatory functions of the rostral ventromedial medulla (RVM) in the lightly anesthetized rat. Microinjection of selective GABA_A receptor antagonists bicuculline methiodide and SR95531 produced a significant increase in tail-flick (TF) latency. This antinociception was dose related, showed recovery and was attenuated by prior injection of the GABA_A receptor agonist THIP at the same site. Microinjection of saline or the glycine receptor antagonist strychnine did not significantly affect TF latency. In contrast, administration of GABA_A receptor agonists THIP and muscimol resulted in a significant decrease in TF latency. Microinjections at sites surrounding the RVM did not significantly affect TF latency. These results demonstrate that a GABA-mediated process within the RVM is crucial in permitting execution of the TF and, presumably, other spinal nociceptive reflexes.