Zhang Hong, He Wei, Hu Xue-Fei, Li Yan-Zhen, Liu Yong-Min, Ge Wen-Qiang, Zhanmu Ou-Yang, Chen Chao, Lan Yu-Ye, Su Yang-Shuai, Jing Xiang-Hong, Zhu Bing, Pan Hui-Lin, Yu Ling-Ling, Li Man
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Research Center of Meridians, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Mar 25;13:861799. doi: 10.3389/fphar.2022.861799. eCollection 2022.
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 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.
炎症性肠病（IBD）会导致患者慢性腹痛，这是由于结肠中存在炎症反应。电针（EA）可有效减轻与IBD相关的内脏疼痛和结肠炎症。大麻素CB2受体激动剂在IBD小鼠模型中也能减轻结肠炎症。然而，电针是否通过CB2受体减轻内脏疼痛和结肠炎症仍不清楚。在此，我们确定了在通过直肠灌注2,4,6-三硝基苯磺酸溶液（TNBS）诱导的IBD小鼠模型中电针的抗伤害感受作用机制。连续七天在双侧大肠俞（BL25）穴位进行电针或假电针。进行von Frey和结肠扩张试验以测量机械性牵涉痛和内脏疼痛。进行蛋白质免疫印迹和免疫组织化学分析以确定结肠组织中IL-1β和诱导型一氧化氮合酶（iNOS）的表达以及巨噬细胞的活化情况。我们发现，电针而非假电针可减轻内脏超敏反应并促进CB2受体的活化，进而抑制巨噬细胞活化以及IL-1β和iNOS的表达。电针的作用被特异性CB2受体拮抗剂AM630以及CB2受体基因敲除所阻断。我们的研究结果表明，电针通过激活CB2受体并随后抑制巨噬细胞活化以及IL-1β和iNOS的表达，减轻与IBD相关的机械性异常性疼痛和内脏超敏反应。
