Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2024; 30(10): 1431-1449
Published online Mar 14, 2024. doi: 10.3748/wjg.v30.i10.1431
Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome
Zheng-Yang Li, Yu-Qing Mao, Qian Hua, Yong-Hong Sun, Hai-Yan Wang, Xuan-Guang Ye, Jing-Xian Hu, Ya-Jie Wang, Miao Jiang
Zheng-Yang Li, Qian Hua, Hai-Yan Wang, Jing-Xian Hu, Ya-Jie Wang, Miao Jiang, Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai 201508, China
Yu-Qing Mao, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Yong-Hong Sun, Department of Gastroenterology, Dalian Friendship Hospital, Dalian 116001, Liaoning Province, China
Xuan-Guang Ye, Department of Pathology, Jinshan Hospital of Fudan University, Shanghai 201508, China
Co-corresponding authors: Ya-Jie Wang and Miao-Jiang.
Author contributions: Li ZY contributed to the research concept, animal surgery and behavioral studies, data analysis and interpretation, drafting of the manuscript; Mao YQ contributed to the animal surgery and behavioral studies; Hua Q contributed to the study supervision, participant enrollment, and supplementary experimental support; Sun YH contributed to the participant enrollment, analysis and technical and material support; Ye XG contributed to the acquisition of data, statistical analysis and technical support; Hu JX contributed to the study supervision, acquisition of data; Wang HY contributed to the acquisition of data, statistical analysis; Jiang M and Wang YJ contributed to the research concept, supervision of studies, critical revision of the manuscript.
Supported by The Health Commission of Jinshan District, Shanghai, China, No. JSKJ-KTMS-2019-01; The Youth Research Foundation of Jinshan Hospital of Fudan University, No. JYQN-JC-202101 and No. JYQN-JC-202216; and The Reserve Discipline Construction of Jinshan Hospital of Fudan University, No. HBXK-2021-2.
Institutional review board statement: The use of human tissue samples and clinical data was approved by the ethics committee of Dalian Friendship Hospital. All donors were informed of the aim of the study and gave consent to donate their samples.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Institutional animal care and use committee statement: This study was approved by the Fudan University School of Medicine Animal Care and Use Committee and was performed in accordance with the guidelines of the International Association for the Study of Pain.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest. Patient consent was obtained.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author from the Department of Gastroenterology, Jinshan Hospital of Fudan University, Number 1508, Longhand Road, Jinshan District, Shanghai, 201508, People’s Republic of China
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Miao Jiang, PhD, Researcher, Department of Gastroenterology, Jinshan Hospital of Fudan University, No. 1508 Longhand Road, Jinshan District, Shanghai 201508, China. jiangmiao_@fudan.edu.cn
Received: November 27, 2023
Peer-review started: November 27, 2023
First decision: December 12, 2023
Revised: December 29, 2023
Accepted: February 6, 2024
Article in press: February 6, 2024
Published online: March 14, 2024
Processing time: 108 Days and 4.1 Hours
ARTICLE HIGHLIGHTS
Research background

Patients with irritable bowel syndrome with diarrhea (IBS-D) experience a significant reduction in their quality of life. While the exact pathogenesis of IBS-D remains incompletely understood, research indicates that serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The role of 5-HT2B receptor in the altered gut sensation of IBS-D was not investigated.

Research motivation

This study is to identify the role of 5-HT2B receptor in the altered gut sensation via transient receptor potential vanilloid type 1 (TRPV1) channels in rat model and patients with diarrhea-predominant IBS.

Research objectives

This study aims to elucidate the role of the 5-HT2B receptor in both IBS-D patients and rat models induced by acetic acid and wrap restraint. The findings are anticipated to offer novel insights into potential avenues for IBS-D treatment.

Research methods

Rectosigmoid biopsies were collected from IBS-D patients and healthy controls. The expression level of 5-HT2B receptor in colon tissue was measured and correlated with abdominal pain scores in IBS-D patients. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity, 5-HT2B receptor and TRPV1 expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after the administration of the TRPV1 antagonist were recorded.

Research results

A higher expression of 5-HT2B receptor was observed in the colonic mucosa of patients with IBS-D compared to controls, correlating with abdominal pain scores. The IBS-D rats was successfully established through intracolonic instillation of acetic acid and wrap restraint. Administration of the exogenous 5-HT2B receptor agonist increased visceral hypersensitivity, which was subsequently alleviated by successive administration of TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist displayed inhibition of visceral hyperalgesia. Additionally, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats significantly decreased with the administration of 5-HT2B receptor antagonist.

Research conclusions

The increased expression of 5-HT2B receptor contributing to visceral hyperalgesia through the induction of TRPV1 expression in IBS-D, providing important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.

Research perspectives

The analgesic effect of RS-127445 in IBS-D rats suggests its potential as a novel treatment for IBS-D.