Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Department of Biology, School of Basic Sciences, University of Zabol, Po. Box: 98615-538, Zabol, 9861335856, Iran.
Psychopharmacology (Berl). 2021 Jun;238(6):1657-1669. doi: 10.1007/s00213-021-05800-3. Epub 2021 Mar 13.
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.
Considering the abundance of GABA 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 receptor agonist, muscimol, and the GABA receptor antagonist, bicuculline, on pain modulation using formalin test. We also assessed interaction between canabinergic and GABAergic systems in the NC during this test.
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.
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.
This study shows that GABA in the NC is involved in pain modulation and suggests the existence of a GABA-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 receptors in the NC.
楔状核（NC）是中脑的网状核，是下行疼痛调制系统的一部分，因此在疼痛感知中起重要作用。
鉴于 NC 中 GABA 和大麻素受体丰富，以及 GABA 在控制伤害感受中的双向作用，本研究使用福尔马林试验检查了双侧 NC 内微注射不同剂量的 GABA 受体激动剂 muscimol 和 GABA 受体拮抗剂 bicuculline 对疼痛调制的影响。我们还在该试验中评估了 NC 中大麻素能和 GABA 能系统之间的相互作用。
将大鼠暴露于 NC 内微注射 bicuculline（50、100 和 200 ng/侧）或 muscimol（60、120 和 240 ng/侧），然后进行福尔马林试验。在另一组实验中，评估了 muscimol（60 ng/侧）或 bicuculline（50 ng/侧）给药 5 分钟后，大麻素受体激动剂 WIN 55,212-2（5、10 和 20 μg/侧）微注射到 NC 对福尔马林试验的影响。
NC 内微注射 bicuculline 和 muscimol 以剂量依赖性方式分别降低和增加测试的两个阶段的疼痛反应。NC 内微注射 WIN 55,212-2 以剂量依赖性方式显著降低疼痛反应。NC 内微注射 bicuculline 或 muscimol 与 WIN 55,212-2 联合注射分别增强和减弱了福尔马林试验中 WIN 55,212-2 诱导的抗伤害作用。
本研究表明 NC 中的 GABA 参与疼痛调制，并表明 NC 中存在 GABA 介导的抑制系统对疼痛控制。此外，WIN 55,212-2 在福尔马林试验中的镇痛作用似乎部分通过 NC 中局部 GABA 受体的活性介导。
