Role of GABA in activation and mechanism of antinociceptive system.

研究了氨基丁酸（GABA_A）受体拮抗剂picrotoxin （PTX）静脉注射对氨基丁酸（GABA_A）受体拮抗剂猫腰椎脊髓宽动态范围（WDR）神经元活性的影响。静脉注射PTX增强了WDR神经元的触觉诱发反应，但减少了伤害性反应，且呈剂量依赖性。脊髓横断逆转了伤害性反应的抑制。在脊髓猫中，静脉注射PTX增强了触觉诱发反应。静脉注射PTX增强中缝背核（NRD）和/或腹侧输水导管周围灰质（PAG）神经元投射到中缝大核的自发放电。NRD/PAG内注射利多卡因可逆转静脉注射PTX的抗痛觉作用。PTX注入NRD/PAG可降低WDR单位的热诱发反应。静脉注射微螺毒素后，NRD和PAG中可见c- fos样免疫反应神经元。蜂毒皮下注射前静脉注射PTX可显著提高脊髓背角V层c- fos样免疫反应性的表达。这些数据表明，静脉注射PTX的抗痛觉作用主要是由于源自NRD和PAG的下行抗痛觉系统的去抑制激活，并且PTX增强了脊髓中触摸诱发的反应。

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.