Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2021; 27(30): 5060-5075
Published online Aug 14, 2021. doi: 10.3748/wjg.v27.i30.5060
Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress
Jing-Hong Chen, Ying Sun, Pei-Jun Ju, Jin-Bao Wei, Qing-Jie Li, John H Winston
Jing-Hong Chen, Ying Sun, Pei-Jun Ju, Jin-Bao Wei, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Jing-Hong Chen, Qing-Jie Li, John H Winston, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, United States
Author contributions: Chen JH and Winston JH contributed to the concept and design of the experiments; Chen JH performed the experiments; Chen JH, Sun Y, Ju PJ, Wei JB, Li QJ and Winston JH analyzed the data and prepared the paper.
Supported by NIDDK, No. 5R01DK111819-03 and No. 5R01DK032346-28; National Natural Science Foundation of China, No. 81571326.
Institutional review board statement: The study was undertaken with the approval of the Institutional Animal Care and Use Committee of the University of Texas Medical Branch at Galveston, TX, United States.
Institutional animal care and use committee statement: The study was undertaken with the approval of the Institutional Animal Care and Use Committee of the University of Texas Medical Branch at Galveston, TX.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: John H Winston, PhD, Professor, Department of Internal Medicine, University of Texas Medical Branch, 8-104 Med Res Bldg, Galveston, TX 77555, United States. jhwinsto@utmb.edu
Received: March 4, 2021
Peer-review started: March 4, 2021
First decision: May 5, 2021
Revised: May 19, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: August 14, 2021
Core Tip

Core Tip: We investigated whether estrogen re-enhanced visceral hyperalgesia in chronic prenatal stress plus chronic adult stress models. After using physical ovariectomy or chemical inhibition with letrozole to reduce estrogen levels, we found that visceral hyperalgesia, colonic afferent neuronal excitability, nerve growth factor and brain-derived neurotrophic factor, and estrogen were all increased. The findings indicate that chronic stress-induced visceral hypersensitivity was estrogen dependent and that the hypersensitivity was mediated by estrogen-dependent sensitization of primary afferent colon neurons. The preclinical models provide key scientific evidence in support of developing gender-based visceral pain management.