Role of GABA in activation and mechanism of antinociceptive system.

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Effects of intravenous administration of picrotoxin (PTX), a GABA_A receptor antagonist, upon activities of wide dynamic range (WDR) neurons in the lumbar spinal cord were studied in urethane-chloralose anesthetized cats. Intravenous PTX augmented tactile evoked responses of WDR neurons, but reduced nociceptive responses, dose-dependently. Spinal transection reversed the suppression of nociceptive responses. In the spinal cat, intravenous PTX enhanced the tactile evoked response. Intravenous PTX enhanced the spontaneous firing of nucleus raphe dorsalis (NRD) and/or ventral periaqueductal gray (PAG) neurons projecting to nucleus raphe magnus. Lidocaine injected into NRD/PAG reversed the antinociceptive action of intravenous PTX.PTX injected into NRD/PAG reduced heat-evoked responses of WDR units. Following intravenous picrotoxin administration, c-Fos-like immunoreactive neurons were found in the NRD and PAG.Intravenous PTX prior to the subcutaneous bee venom significantly increased the expression of c-Fos-like immunoreactivity in lamina V of spinal dorsal horn. These data suggest that antinociceptive effects of intravenous PTX is primarily due to disinhibitory activation of the descending antinociceptive system originating from NRD and PAG,and that PTX reinforces touch-evoked responses in the spinal cord.