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鞘内注射γ-氨基丁酸(GABA)激动剂在脊髓水平的抗伤害感受作用

[Antinociceptive effects of intrathecally administered GABA agonists at the spinal cord level].

作者信息

Yamada Y, Saito Y, Hara K, Kirihara Y, Doi K, Kosaka Y

机构信息

Department of Anesthesiology, Shimane Medical University, Izumo.

出版信息

Masui. 1999 Jun;48(6):605-10.

Abstract

The present study was designed to investigate antinociceptive effect of GABA agonists regarding visceral as well as somatic noxious stimuli. Following the approval by the institutional animal care committee, an intrathecal catheter was implanted in the subarachnoid space at the L 4/5 level in male Sprague-Dawley rats. The tail flick (TF) test and the colorectal distension test (CD) were used to measure responses to somatic and visceral stimuli, respectively. Threshold in TF test and CD test were measured at 5, 10, 15, 20, 30, 60, 90, 120 and 180 min after the intrathecal injection of 0.1, 1, 5, 20 micrograms of muscimol, 0.01, 0.1, 0.3, 1 microgram of baclofen or normal saline. Percent of maximum possible effect (%MPE) and %area under the curve (%AUC) were calculated by transforming response threshold in TF and CD tests. Repeated measure ANOVA followed by Fisher's PLSD test were used for statistical analysis. Muscimol 0.1 microgram increased mean %MPE in TF test at 10 min to 15% but not in CD test. Muscimol 1, 5 and 20 micrograms significantly increased %MPE at 5 min in TF and CD tests. Muscimol 20 micrograms produced 100%MPE for 180 min after drug injection. Baclofen 0.1, 0.3 and 1 microgram significantly increased %MPE at 5 min in TF and CD test. Antinociceptive effect in TF test seems to be greater than that in CD test. Muscimol caused motor disturbance but baclofen did not. It is concluded that intrathecally administered muscimol and baclofen produced somatic and visceral antinociception in a dose dependent fashion.

摘要

本研究旨在探讨γ-氨基丁酸(GABA)激动剂对内脏及躯体伤害性刺激的抗伤害感受作用。经机构动物护理委员会批准后,在雄性Sprague-Dawley大鼠的L 4/5水平蛛网膜下腔植入鞘内导管。分别采用甩尾(TF)试验和结直肠扩张试验(CD)来测量对躯体和内脏刺激的反应。在鞘内注射0.1、1、5、20微克蝇蕈醇、0.01、0.1、0.3、1微克巴氯芬或生理盐水后5、10、15、20、30、60、90、120和180分钟测量TF试验和CD试验的阈值。通过转换TF和CD试验中的反应阈值来计算最大可能效应百分比(%MPE)和曲线下面积百分比(%AUC)。采用重复测量方差分析,随后进行Fisher最小显著差异检验进行统计分析。0.1微克蝇蕈醇在TF试验中10分钟时使平均%MPE增加至15%,但在CD试验中未增加。1、5和20微克蝇蕈醇在TF和CD试验中5分钟时显著增加%MPE。20微克蝇蕈醇在注射药物后180分钟产生100%MPE。0.1、0.3和1微克巴氯芬在TF和CD试验中5分钟时显著增加%MPE。TF试验中的抗伤害感受作用似乎大于CD试验中的作用。蝇蕈醇引起运动障碍,但巴氯芬未引起。得出的结论是,鞘内注射蝇蕈醇和巴氯芬以剂量依赖方式产生躯体和内脏抗伤害感受作用。

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