Vagus Nerve Stimulation Relives Irritable Bowel Syndrome and the Associated Depression via α7nAChR-mediated Anti-inflammatory Pathway

Qizhi Yan; Jiawei Chen; Xiuying Ren; Yibo Song; Jian Xu; Shaoyan Xuan; Xi Jiang; Zhijian Kuang; Zhihua Tang

doi:10.1016/j.neuroscience.2023.08.026

Vagus Nerve Stimulation Relives Irritable Bowel Syndrome and the Associated Depression via α7nAChR-mediated Anti-inflammatory Pathway

Neuroscience. 2023 Oct 15:530:26-37. doi: 10.1016/j.neuroscience.2023.08.026. Epub 2023 Aug 23.

Authors

Qizhi Yan¹, Jiawei Chen¹, Xiuying Ren¹, Yibo Song¹, Jian Xu¹, Shaoyan Xuan¹, Xi Jiang², Zhijian Kuang², Zhihua Tang³

Affiliations

¹ Shaoxing People's Hospital, Shaoxing 312000, China.
² Zhejiang University Mingzhou Hospital, Ningbo 315000, China.
³ Shaoxing People's Hospital, Shaoxing 312000, China. Electronic address: tangzhihua_2015@163.com.

PMID: 37625687
DOI: 10.1016/j.neuroscience.2023.08.026

Abstract

Objectives: The present study is designed to investigate the role of vagus nerve in the treatments of irritable bowel syndrome (IBS) and the associated central nervous system disorders.

Methods: An IBS animal model was established by giving acetic acid and chronic-acute stress (AA-CAS) treatment in adult male Wistar rats. Subdiaphragmatic vagotomy (SDV) and vagus nerve stimulation (VNS) were performed to intervene the excitability of vagus nerve. Permeability of blood brain barrier (BBB) was measured and agonist and antagonist of α7 nicotinic acetylcholine receptor (α7nAChR) were used to explore the relevant mechanisms.

Results: AA-CAS treatment resulted in abnormal fecal output, increased visceral sensitivity, depressive-like behaviors, and overexpression of inflammatory mediators, all of which were reversed by VNS treatment. The effects of VNS could also be observed when α7nAChR agonist was applied. Whereas α7nAChR antagonist (methyllycaconitine, MLA) reversed VNS's effects. Interestingly, VNS also reduced the increased permeability of blood brain barrier (BBB) following AA-CAS treatment in IBS rats. SDV treatment only show temporary efficacy on AA-CAS-induced symptoms and had no effect on the permeability of BBB.

Conclusion: The intestinal abnormalities and depressive symptoms in IBS rats can be improved by VNS treatment. This positive effect of VNS was achieved through α7nAChR-mediated inflammatory pathway and may also be associated with the decreased of BBB permeability.

Keywords: depression; inflammation; irritable bowel syndrome; vagus; α7nAChR.