内源性大麻素在阿立哌唑外周抗伤害作用中的研究
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Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole
背景与目的
研究表明抗精神病药物多巴胺能和5-羟色胺能激动剂阿立哌唑诱导外周抗伤害作用。然而，这一效应的机制尚未完全清楚。本研究旨在确定阿立哌唑的这种作用与内源性大麻素系统之间的关系。
方 法
所有药物均以20μL的体积局部注射于体重30~35g的雄性瑞士小鼠右后足，足底注射前列腺素E2(2μg)诱发痛觉过敏。在测量前10分钟注射阿立哌唑，并在阿立哌唑前10分钟给予阿立哌唑不可逆抑制剂(MAFP)、单酰甘油脂肪酶抑制剂(JZL184)和大麻素再摄取抑制剂(VDM11)。在注射前列腺素E2后的第三小时使用痛觉测量仪测量痛觉阈值。用方差分析和Bonferroni检验进行数据分析。
结 果
阿立哌唑(100μg)的抗伤害作用可被大麻素1或2受体拮抗剂AM251(40μg[P<.01]，80μg[P<.0001]和160μg[P<.0001])和AM630(100μg[P<.0001]，200μg[P<.0001]和400μg[P<.0001]))阻断。阿立哌唑(25μg)引起的外周抗伤害作用可被脂肪酸酰胺水解酶抑制剂(MAFP0.5μg[P<.0001])或单酰甘油脂肪酶抑制剂(JZL184，4μg[P<.0001])增强。此外，大麻素再摄取抑制剂(VDM11，2.5μg[P<.0001])也观察到类似的增强作用。
结 论
这些结果为内源性大麻素系统参与阿立哌唑治疗引起的外周抗伤害作用提供了证据。
原始文献摘要
Renata C. M. Ferreira, MSc, Ana F. Almeida-Santos, et al.Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole: Anesth Analg 2019;129:263–268
BACKGROUND: Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established. Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system.
METHODS: All drugs were given locally into the right hind paw of male Swiss mice weighing 30–35 g in a volume of 20 μL. The hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2 μg). Aripiprazole was injected 10 minutes before the measurement, and an irreversible inhibitor of anandamide hydrolase (MAFP), an inhibitor for monoacylglycerol lipase (JZL184), and an anandamide reuptake inhibitor (VDM11) were given 10 minutes before the aripiprazole. Nociceptive thresholds were measured using an algesimetric apparatus in the third hour after prostaglandin E2 injection. Data were analyzed by ANOVA and Bonferroni tests.
RESULTS: The antinociceptive effect induced by aripiprazole (100 μg) was blocked by cannabinoid 1 or 2 receptor antagonists AM251 (40 μg [P < .01], 80 μg [P < .0001], and 160 μg [P < .0001]) and AM630 (100 μg [P < .0001], 200 μg [P < .0001], and 400 μg [P < .0001]), respectively. The peripheral antinociception induced by aripiprazole (25 μg) was enhanced by administration of the inhibitor of fatty acid amide hydrolase (MAFP, 0.5 μg [P < .0001]) or monoacylglycerol lipase (JZL184, 4 μg [P < .0001]). Moreover, a similar enhancement was observed with the anandamide reuptake inhibitor (VDM11, 2.5 μg [P < .0001]).
CONCLUSIONS: These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.
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贵州医科大学高鸿教授课题组
翻译：余晓旭 编辑：何幼芹 审校：王贵龙