Department of Physiology and Pathophysiology, Faculty of Medicine, Medical University, 1403 Sofia, Bulgaria.
Department of Anatomy, Faculty of Medicine, Medical University, 1606 Sofia, Bulgaria.
Int J Mol Sci. 2023 Feb 2;24(3):2886. doi: 10.3390/ijms24032886.
The effects on stress-induced analgesia (SIA) from endogenous cannabinoid system (ECS) and nitric oxide (NO) interaction after 1 h of restraint stress were evaluated in male Wistar rats. The animals were subjected to 1 h of restraint and then injected with different combinations of cannabinoid receptor type 1 agonist anandamide (AEA) or antagonist AM251 along with an NO donor, NO precursor, or inhibitor of NO synthase. Nociception was evaluated using paw pressure (PP) or hot plate (HP) tests. AEA was administered immediately after the end of restraint-SIA (r-SIA). Administration of NO precursor reversed the pronociceptive effect of the CB1 agonist on r-SIA. Both the CB1 antagonist and the NOS inhibitor neutralized the pro-analgesic effect of L-arginine (L-arg). Administration of an NO donor, instead, increased r-SIA. Our experiments confirmed that the endogenous cannabinoid and the NO-ergic systems interact in the modulation of r-SIA. This interaction probably implies NO as a second messenger of the ECS.
在 1 小时束缚应激后，评估内源性大麻素系统 (ECS) 和一氧化氮 (NO) 相互作用对应激诱导镇痛 (SIA) 的影响，雄性 Wistar 大鼠。动物被束缚 1 小时，然后注射不同组合的大麻素受体 1 激动剂大麻素（AEA）或拮抗剂 AM251 以及一氧化氮供体、NO 前体或一氧化氮合酶抑制剂。使用足底压力 (PP) 或热板 (HP) 试验评估痛觉。AEA 在束缚结束后立即给药-SIA（r-SIA）。NO 前体的给药逆转了 CB1 激动剂对 r-SIA 的致痛作用。CB1 拮抗剂和 NOS 抑制剂均中和了 L-精氨酸 (L-arg) 的抗痛觉作用。相反，NO 供体的给药增加了 r-SIA。我们的实验证实，内源性大麻素和 NO 能系统在调节 r-SIA 中相互作用。这种相互作用可能意味着 NO 作为 ECS 的第二信使。
