Basic Study
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World J Gastroenterol. Mar 21, 2025; 31(11): 98974
Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.98974
NMDAR2B/PKA/CREB signaling pathway contributes to esophageal neuropathic pain in gastroesophageal reflux disease
Yi Wang, Guan-Wu Li, Sheng-Liang Zhu, Ting-Ting Xu, Yi-Wen Qin, Chuan-Qi Cheng, Qin-Wei Zheng, Cong He, Bing-Duo Zhou, Sheng-Quan Fang
Yi Wang, Sheng-Liang Zhu, Ting-Ting Xu, Yi-Wen Qin, Chuan-Qi Cheng, Qin-Wei Zheng, Cong He, Bing-Duo Zhou, Sheng-Quan Fang, Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Guan-Wu Li, Department of Radiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Co-corresponding authors: Bing-Duo Zhou and Sheng-Quan Fang.
Author contributions: The work presented here was performed in collaboration among all the authors. Zhou BD and Fang SQ identified the research topic; Li GW and Zhu SL designed the methods and experiments; Wang Y, Xu TT and Qin YW performed the laboratory experiments, analyzed the data and interpreted the results; Wang Y wrote the paper; Cheng CQ, Zheng QW and He C drafted and revised the manuscript; all the authors contributed to, read and approved the manuscript. Zhou BD and Fang SQ contributed equally to this work as co-corresponding authors. The reasons for designating Zhou BD and Fang SQ as co-corresponding authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resulting paper. This designation also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team included authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This designation also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Zhou BD and Fang SQ both provided financial support for the research. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution while recognizing the spirit of teamwork and collaboration in this study. In summary, we believe that designating Zhou BD and Fang SQ as co-corresponding authors is appropriate for our manuscript, as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Supported by the National Major Project of Science and Technology for the Prevention and Control of the "Four Major Chronic Diseases", No. 2024ZD0520903; National Natural Science Foundation of China, No. 82004324; the Training Program for High-caliber Talents of Clinical Research at Affiliated Hospitals of SHUTCM; the Training Project for Xinglin Young and Middle-Aged Talents of Shanghai University of Traditional Chinese Medicine, No. SHUTCM HR (2020) 23; the Project of National Famous Traditional Chinese Medicine Expert (Shengliang Zhu) Inheritance Studio, No. NATCM HR (2022) 75; the Zhu Shengliang Academic Experience Research Studio Project of Shanghai Famous Traditional Chinese Medicine, No. SHGZS-202203; and the Shanghai High-Level Talent Leadership Plan for Traditional Chinese Medicine, No. ZY(2021-2023)-0403.
Institutional animal care and use committee statement: Animal welfare and experimental procedures were strictly carried out in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, Washington, DC, 1996) and were approved by the Animal Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (Shanghai, China) in 2023 (reference number YYLAC-2023-230).
Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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: The data generated in this study are available from the corresponding author on reasonable request.
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: Bing-Duo Zhou, PhD, Chief Doctor, Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai 200437, China. bingduozhou@126.com
Received: July 10, 2024
Revised: December 10, 2024
Accepted: February 17, 2025
Published online: March 21, 2025
Processing time: 245 Days and 23 Hours
Core Tip

Core Tip: Esophageal hypersensitivity is a major contributor to refractory gastroesophageal reflux disease (GERD), meaning that minor distension and physiological acid reflux can cause significant discomfort. Given that N-methyl-D-aspartate receptors (NMDARs) may play a crucial role in visceral hypersensitivity in functional gastrointestinal disorders, this study aimed to investigate whether NMDAR2B contributes to esophageal neuropathic pain. Immunohistochemistry, Western blot, RT-PCR and ELISA were used to measure the corresponding protein and mRNA expression levels in the cingulate gyrus, dorsal thalamus, spinal dorsal horn, esophageal tissues and serum of a rat model of esophageal hypersensitivity. Our findings suggest that the NMDAR2B/ protein kinase A/cAMP-response element binding protein signaling pathway contributes to esophageal neuropathic pain in GERD patients.