Role of GABA in activation and mechanism of antinociceptive system.

在氯醛糖麻醉猫上观察了GABA_A受体拮抗剂印防己毒素（PTX）对腰髓宽动态范围（WDR）神经元活动的影响。静脉注射PTX可增强WDR神经元的触觉诱发反应，但降低伤害性反应，呈剂量依赖性。脊髓横断可逆转对伤害性反应的抑制。在脊髓猫，静脉注射PTX增强触觉诱发反应。静脉注射PTX可增强中缝背核（NRD）和/或中脑导水管周围灰质（PAG）神经元向中缝大核投射的自发放电。NRD/PAG内注入利多卡因可逆转静脉注射PTX的抗伤害作用，而NRD/PAG内注入PTX可减少WDR单位的热诱发反应。静脉注射印防己毒素后，在NRD和PAG内发现c-Fos样免疫反应阳性神经元，在皮下注射蜂毒前静脉注射PTX可显著增加脊髓背角V层c-Fos样免疫反应阳性神经元的表达。这些数据表明，静脉注射PTX的抗伤害性作用主要是由于去抑制激活的下行抗伤害性系统起源于NRD和PAG，PTX加强触摸诱发的脊髓反应。

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.