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

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 col...

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Main Authors: Hong Zhang, Wei He, Xue-Fei Hu, Yan-Zhen Li, Yong-Min Liu, Wen-Qiang Ge, Ou-Yang Zhanmu, Chao Chen, Yu-Ye Lan, Yang-Shuai Su, Xiang-Hong Jing, Bing Zhu, Hui-Lin Pan, Ling-Ling Yu, Man Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.861799/full
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author Hong Zhang
Wei He
Xue-Fei Hu
Yan-Zhen Li
Yong-Min Liu
Wen-Qiang Ge
Ou-Yang Zhanmu
Chao Chen
Yu-Ye Lan
Yang-Shuai Su
Xiang-Hong Jing
Bing Zhu
Hui-Lin Pan
Ling-Ling Yu
Man Li
author_facet Hong Zhang
Wei He
Xue-Fei Hu
Yan-Zhen Li
Yong-Min Liu
Wen-Qiang Ge
Ou-Yang Zhanmu
Chao Chen
Yu-Ye Lan
Yang-Shuai Su
Xiang-Hong Jing
Bing Zhu
Hui-Lin Pan
Ling-Ling Yu
Man Li
author_sort Hong Zhang
collection DOAJ
description 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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spelling doaj.art-873c32d2de294336a1eef9a594833cc02022-12-22T02:39:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.861799861799Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel DiseaseHong Zhang0Wei He1Xue-Fei Hu2Yan-Zhen Li3Yong-Min Liu4Wen-Qiang Ge5Ou-Yang Zhanmu6Chao Chen7Yu-Ye Lan8Yang-Shuai Su9Xiang-Hong Jing10Bing Zhu11Hui-Lin Pan12Ling-Ling Yu13Man Li14Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaResearch Center of Meridians, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaResearch Center of Meridians, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, ChinaResearch Center of Meridians, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, ChinaResearch Center of Meridians, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInflammatory 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.861799/fullelectroacupuntureinflammatory bowel diseaseCB2 receptorvisceral painmacrophage
spellingShingle Hong Zhang
Wei He
Xue-Fei Hu
Yan-Zhen Li
Yong-Min Liu
Wen-Qiang Ge
Ou-Yang Zhanmu
Chao Chen
Yu-Ye Lan
Yang-Shuai Su
Xiang-Hong Jing
Bing Zhu
Hui-Lin Pan
Ling-Ling Yu
Man Li
Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
Frontiers in Pharmacology
electroacupunture
inflammatory bowel disease
CB2 receptor
visceral pain
macrophage
title Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
title_full Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
title_fullStr Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
title_full_unstemmed Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
title_short Electroacupuncture Reduces Visceral Pain Via Cannabinoid CB2 Receptors in a Mouse Model of Inflammatory Bowel Disease
title_sort electroacupuncture reduces visceral pain via cannabinoid cb2 receptors in a mouse model of inflammatory bowel disease
topic electroacupunture
inflammatory bowel disease
CB2 receptor
visceral pain
macrophage
url https://www.frontiersin.org/articles/10.3389/fphar.2022.861799/full
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