Rationale

Nucleus cuneiformis (NC), a reticular nucleus of the midbrain, is a part of the descending pain modulatory system and therefore has an important role in pain perception.

Objectives

Considering the abundance of GABA_A and cannabinoid receptors in the NC and also the bidirectional roles for GABA in controlling nociception, the present study examined the effects of bilateral intra-NC microinjection of different doses of the GABA_A receptor agonist, muscimol, and the GABA_A receptor antagonist, bicuculline, on pain modulation using formalin test. We also assessed interaction between canabinergic and GABAergic systems in the NC during this test.

Methods

Rats were exposed to intra-NC microinjection of bicuculline (50,100, and 200 ng/side) or muscimol (60, 120, and 240 ng/side) and then subjected to the formalin test. In another set of experiments, the effects of muscimol (60 ng/side) or bicuculline (50 ng/side) administration 5 min before a cannabinoid receptor agonist WIN 55,212-2 (5, 10, and 20 μg/side) microinjection into NC on the formalin test were evaluated.

Results

Microinjection of bicuculline and muscimol into the NC decreased and increased pain responses, respectively, in a dose-dependent manner during both phases of the test. Microinjection of WIN 55,212-2 into the NC significantly reduced pain responses in a dose-dependent manner. Microinjection of bicuculline or muscimol in combination with WIN 55,212-2 into the NC respectively potentiated and attenuated WIN 55,212-2–induced antinociception in the formalin test.

Conclusions

This study shows that GABA in the NC is involved in pain modulation and suggests the existence of a GABA_A-mediated inhibitory system in the NC on pain control. Furthermore, it seems that the antinociceptive effect of WIN 55,212-2 in the formalin test is mediated partly by the activity of local GABA_A receptors in the NC.

中文翻译：

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使用福尔马林测试，楔形核中GABAA受体对大麻素镇痛作用的影响

基本原理

楔形神经核（NC）是中脑的网状核，是下行疼痛调节系统的一部分，因此在疼痛感知中具有重要作用。

目标

考虑到NC中GABA _A和大麻素受体的丰度以及GABA在控制伤害感受中的双向作用，本研究研究了不同剂量的GABA _A受体激动剂，麝香酚和GABA的双侧NC内显微注射的作用。使用福尔马林测试对疼痛调节的_一种受体拮抗剂，比库林（bicuculline）。在此测试中，我们还评估了NC中canananergic和GABAergic系统之间的相互作用。

方法

大鼠接受双小分子（50,100和200 ng /侧）或麝香酚（60、120和240 ng /侧）的NC内显微注射，然后进行福尔马林测试。在另一组实验中，在将大麻素受体激动剂WIN 55,212-2（5、10和20μg/侧）显微注射至NC前5分钟施用muscimol（60 ng /侧）或双小分子（50 ng /侧）的效果对福尔马林测试进行了评估。

结果

在测试的两个阶段中，以微剂量方式分别将双小分子和麝香酚微注射到NC中，从而减轻和增加了疼痛反应。将WIN 55,212-2微注射到NC中，以剂量依赖性方式显着降低了疼痛反应。在福尔马林试验中，将小分子或麝香酚与WIN 55,212-2组合微注射到NC中，分别增强和减弱了WIN 55,212-2诱导的镇痛作用。

结论

这项研究表明，NC中的GABA参与了疼痛调节，并提示了NC中存在GABA _A介导的疼痛控制抑制系统。此外，似乎在福尔马林试验中，WIN 55,212-2的抗伤害感受作用部分是由NC中的局部GABA _A受体的活性介导的。