Role of GABA in activation and mechanism of antinociceptive system.

GABA 在镇痛系统激活和机制中的作用。

• 批准号: 07680889
• 负责人: KOYAMA Natsu
• 金额: $ 1.47万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680889/
• 关键词: GABA_A receptor antagonists; Picrotoxin; antinociception; allodynia; wide dynamic range neuron; periaqueductal gray; nucleus raphe dorsalis; Fos-like immunoreactive neurons; c-FOS; 脊髄

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.

本文观察了静脉注射GABA_A受体拮抗剂印防己毒素(PTX)对乌拉坦-氯醛糖麻醉猫腰髓宽动态范围(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，并呈剂量依赖性。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可增强投射至中缝大核的中缝背核(NRD)和/或中脑导水管周围灰质(PAG)神经元的自发放电。NRD/PAG内注射利多卡因可逆转静脉注射PTX的抗伤害性反应，NRD/PAG内注射PTX可降低WDR单位的热诱发反应。静脉注射印防己毒素后，在NRD和PAG内可见c-Fos免疫反应阳性神经元。经皮下注射蜂毒前静脉注射PTX可显著增强脊髓背角V层c-Fos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抑制了NRD和PAG下行的抗伤害性感受系统，并且PTX增强了脊髓的触摸诱发反应。

项目成果

Koyama N: "Does intravenous administration of GABA receptor antagonists induce both descending antinociceptive and touch-evoked allodynia?" Pain.

Koyama N：“静脉注射 GABA 受体拮抗剂是否会引起下行镇痛作用和触摸诱发的异常性疼痛？”

Natsu Koyama,Fumihiko Hanai,Jun Chen and Toshikatsu Yokota: "Actiration of descending antinaciceptive system produced by intra venous picrotoxin" PAIN RESEARCH. 11. (1996)

Natsu Koyama、Fumihiko Hanai、Jun Chen 和 Toshikatsu Yokota：“静脉内印防己毒素产生的下行抗痛系统的激活”疼痛研究。

Koyama N: "Activation of descending antinociceptive system produced by intravenous Picrotoxin" Pain Research. 11. 85-95 (1996)

Koyama N：“静脉注射印防己毒素产生的下行抗伤害系统的激活”疼痛研究。

Koyama N,Hanai F,Chen J & Yokota T.: "Activation of descending antinociceptive system produced by intravenous Picrotoxin." Pain Res. 11. 85-95 (1996)

小山N,花井F,陈杰

Koyama N,Hanai F & Yokota T.: "Does intravenous administration of GABA_A receptor antagonists induce both descending antinociceptive and touch-evoked allodynia?" Pain. (In Press).

小山 N,花内 F