Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease.

Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease.
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DOI:
10.3389/fphar.2022.861799
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发表时间:
2022
影响因子:
5.6
通讯作者:
Li M
Li M
中科院分区:
医学2区
文献类型:
--
作者:
Zhang H;He W;Hu XF;Li YZ;Liu YM;Ge WQ;Zhanmu OY;Chen C;Lan YY;Su YS;Jing XH;Zhu B;Pan HL;Yu LL;Li M

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炎症性肠病(IBD)由于结肠中存在炎症反应而导致患者的慢性腹痛。电针对IBD内脏痛和结肠炎症有明显的缓解作用。大麻素CB 2受体激动剂还减少IBD小鼠模型中的结肠炎症。然而,EA是否通过CB 2受体减少内脏疼痛和结肠炎症仍然未知。在这里,我们确定了EA的抗伤害性作用的机制,在IBD小鼠模型由直肠灌注的2,4,6-三硝基苯磺酸溶液(TNBS)。电针或假电针双侧大肠俞穴,连续7天。进行von Frey和结直肠扩张试验以测量机械性牵涉痛和内脏痛。采用Western blotting和免疫组织化学方法检测结肠组织中IL-1β和iNOS的表达及巨噬细胞的活化。结果表明,电针可减轻内脏高敏感性,促进CB 2受体的激活,进而抑制巨噬细胞的活化及IL-1β和iNOS的表达,而假电针则无此作用。电针的作用可被特异性CB 2受体拮抗剂AM 630和CB 2受体敲除阻断。我们的研究结果表明,EA通过激活CB 2受体并随后抑制巨噬细胞活化和IL-1β和iNOS的表达来减轻与IBD相关的机械异常性疼痛和内脏高敏感性。
Inflammatory bowel disease (IBD) results in chronic abdominal pain in patients due to the presence of inflammatory responses in the colon. Electroacupuncture (EA) is effective in alleviating visceral pain and colonic inflammation associated with IBD. Cannabinoid CB2 receptor agonists also reduce colonic inflammation in a mouse model of IBD. However, whether EA reduces visceral pain and colonic inflammation via the CB2 receptor remains unknown. Here, we determined the mechanism of the antinociceptive effect of EA in a mouse model of IBD induced by rectal perfusion of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS). EA or sham EA was performed at the bilateral Dachangshu (BL25) point for seven consecutive days. The von Frey and colorectal distension tests were performed to measure mechanical referred pain and visceral pain. Western blotting and immunohistochemistry assays were carried out to determine the expression of IL-1β and iNOS and activation of macrophages in the colon tissues. We found that EA, but not sham EA, attenuated visceral hypersensitivity and promoted activation of CB2 receptors, which in turn inhibited macrophage activation and the expression of IL-1β and iNOS. The effects of EA were blocked by AM630, a specific CB2 receptor antagonist, and by CB2 receptor knockout. Our findings suggest that EA attenuates mechanical allodynia and visceral hypersensitivity associated with IBD by activating CB2 receptors and subsequent inhibition of macrophage activation and expression of IL-1β and iNOS.
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