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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Electroacupuncture ameliorates visceral hypersensitivity and negative emotions by regulating paraventricular hypothalamic nucleus and colonic corticotropin-releasing factor signaling
Jian-Gang Xu, Yi Yuan, Hong-Kun Ma, Shun Huang, Shan-Lan Zhu, Tan-Ting Li, Xi-Yang Wang, Guo-Ming Shen, Hao Wang
Jian-Gang Xu, Yi Yuan, Shun Huang, Shan-Lan Zhu, Xi-Yang Wang, Guo-Ming Shen, Hao Wang, College of Integrated Chinese and Western Medicine (School of Life Science), Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China
Hong-Kun Ma, College of Acupuncture and Moxibustion, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China
Shan-Lan Zhu, Guo-Ming Shen, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230051, Anhui Province, China
Tan-Ting Li, The First Clinical Medical College, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China
Hao Wang, Anhui Province Key Laboratory of Meridian Viscera Correlationship, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China
Co-first authors: Jian-Gang Xu and Yi Yuan.
Co-corresponding authors: Guo-Ming Shen and Hao Wang.
Author contributions: Wang H, Shen GM and Xu JG designed the all experiments; Xu JG and Yuan Y performed animal experiments such as viral injections and behavioral tests, completed molecular experiments such as Western blot and immunofluorescence, as well as performed the data analysis and visualization; Ma HK, Huang S, Zhu SL and Li TT assisted in the experimental process and helped analyze the data; Wang XY provided guidance on experimental methods and provided overall supervision; Xu JG, Yuan Y and Ma HK wrote the manuscript and drew the figures; Wang H and Shen GM revised the manuscript; Wang H, Shen GM and Wang XY provided financial support and project management; All authors have read and approved the final manuscript. Xu JG and Yuan Y played an important role in the conduct of the experiments and were designated as co-first authors. Shen GM and Wang H were designated as co-corresponding authors for their roles in experimental design and guidance as well as overall management.
Supported by the Excellent Youth Project of Anhui Universities, No. 2022AH030065; National Natural Science Foundation of China, No. 82474224 and No. 82405244; Anhui Provincial Natural Science Foundation, No. 2408085MH223; Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship, No. 2024AHMVC04; Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute, No. 2023CXMMTCM016; and the Anhui Province Scientific Research Planning Project, No. 2022AH050438.
Institutional animal care and use committee statement: All experimental animal procedures were conducted in accordance with the Anhui University of Chinese Medicine Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of Anhui University of Chinese Medicine, No. AHUCM-mouse-2024148.
Conflict-of-interest statement: All authors declare that there is no conflict of interest to disclose.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Corresponding authors at
haohao19870521@126.com may reasonably be asked to provide information about the data in this study.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hao Wang, MD, Associate Professor, College of Integrated Chinese and Western Medicine (School of Life Science), Anhui University of Chinese Medicine, No. 350 Longzihu Road, Hefei 230012, Anhui Province, China.
haohao19870521@126.com
Received: March 21, 2025
Revised: April 24, 2025
Accepted: June 18, 2025
Published online: August 19, 2025
Processing time: 140 Days and 22.3 Hours
BACKGROUND
Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome (IBS) and is often accompanied by negative emotions such as anxiety or depression. Paraventricular hypothalamic nucleus (PVN) corticotropin-releasing factor (CRF) is involved in the stress-related gastrointestinal dysfunction. Electroacupuncture (EA) has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients. However, the underlying mechanisms remain unclear.
AIM
To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS, as well as the effect mechanism of EA.
METHODS
A model of diarrhoeal IBS (IBS-D) with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema. The effect of EA was verified by abdominal withdrawal reflex and open-field test. PVN CRF-colonic mast cell (MC)/transient potential receptor vanilloid type 1 (TRPV1) pathway was detected by immunofluorescence, Western blot, ELISA, and toluidine blue staining. Moreover, PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.
RESULTS
In the model group, IBS-D symptoms and negative emotions were successfully induced. Notably, the combination of Baihui (GV20) with Tianshu (ST25) and Dachangshu (BL25) acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice. Furthermore, we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF, colonic CRF, CRF-receptor 1 (CRF-R1), mast cell tryptase (MCT), protease-activated receptor 2 and TRPV1 in model mice. Moreover, we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice; however, inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1, MCT, and TRPV1.
CONCLUSION
This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
Core Tip: An important feature of functional gastrointestinal disorders (FGIDs) is accompanied with emotional disorders, such as anxiety and depression. Clinically, acupuncture not only improves physical symptoms, but also has a unique psychological effect in treatment of FGIDs. However, the underlying mechanisms remain unclear. Brain-gut crosstalk may mediatepathological process of FGIDs, corticotropin releasing factor (CRF) is an important mediator in brain-gut crosstalk. So, our study focused on the CRF of brain-gut, we hypothesized that electroacupuncture improved mood disorders and visceral pain in irritable bowel syndrome, which may be achieved through paraventricular nucleus CRF-colonic CRF-receptor 1 and downstream pathway.
