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
Abstract
BACKGROUND

Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study.

AIM

To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.

METHODS

Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded.

RESULTS

Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.

Moreover, 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 was significantly reduced by the administration of a 5-HT2B receptor antagonist.

CONCLUSION

Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.

Keywords: Diarrhea-predominant irritable bowel syndrome; Serotonin receptor 2B; Transient receptor potential vanilloid type-1; Visceral hypersensitivity; Abdominal pain

Core Tip: Higher expression of the serotonin receptor 2B (5-HT2B receptor) was found in patients with irritable bowel syndrome with diarrhea (IBS-D) than in that of controls, which was correlated with abdominal pain scores. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a transient receptor potential vanilloid type 1 (TRPV1) antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia. Hence, 5-HT2B receptor-induced visceral hyperalgesia may be mediated by TRPV1 channels, and the analgesic effect of 5-HT2B receptor antagonist could be used as a novel treatment for IBS-D.