NMDAR2B/PKA/CREB signaling pathway contributes to esophageal neuropathic pain in gastroesophageal reflux disease  

作　　者：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 

机构地区：[1]Department of Gastroenterology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China [2]Department of Radiology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China

出　　处：《World Journal of Gastroenterology》2025年第11期100-117,共18页世界胃肠病学杂志(英文)

基　　金：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;the Shanghai High-Level Talent Leadership Plan for Traditional Chinese Medicine,No.ZY(2021-2023)-0403.

摘　　要：BACKGROUND Esophageal hypersensitivity is an important cause of refractory gastroesophageal reflux disease,in which patients do not respond to standard acid-suppressive therapy and suffer from continuous noncardiac chest pain and regurgitation.The N-methyl-D-aspartate receptor(NMDAR)may play a crucial role in the deve-lopment of visceral hypersensitivity in functional gastrointestinal disorders.However,the specific mechanisms of visceral hypersensitivity in upper digestive tract diseases remain poorly understood.AIM To investigate the role of the NMDAR2B/protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway in the development of esophageal neuropathic pain associated with gastroesophageal reflux disease(GERD).METHODS Thirty-six 6-week-old specific pathogen free rats were randomly assigned to six groups:the control,model,model+NMDAR agonist,model+NMDAR anta-gonist,model+PKA antagonist,and model+NMDAR antagonist+PKA agonist groups,with six rats in each group.The model was induced via an intraperitoneal injection of ovalbumin for sensitization along with local esophageal stimulation.Immunohistochemistry and Western blotting were utilized to assess the expression levels of NMDAR2B signaling pathway-related proteins in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and peripheral esophageal tissues.RT-PCR was used to measure the corresponding mRNA expression,and ELISA was used to determine the serum brain-derived neurotrophic factor(BDNF)concentration.Behavioral scoring was performed during balloon distention and acid perfusion of the lower esophagus.RESULTS Compared with the control group,the model group presented significantly increased expression levels of the NMDAR2B,PKA,CREB,BDNF,substance P,and calcitonin gene-related peptide proteins and mRNAs in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and lower esophagus(P<0.05).Compared with the model group,the model+NMDAR agonist group exhibited even higher expression levels of these proteins and mRNAs(P<0.05),whereas the m

关 键 词：Gastroesophageal reflux disease Esophageal hypersensitivity N-METHYL-D-ASPARTATE Brain-derived neurotrophic factor 

分 类 号：R57[医药卫生—消化系统]