文献类型：期刊文献

英文题名：TRPV1-tau axis: A bidirectional regulatory mechanism linking pain sensitization and Alzheimer's disease progression and its potential for intervention

作者：Shi, Liangliang[1,2];Yang, Jin[3];Guo, Yi[2,4,6];Wei, Benjun[1,4];Zhang, Shike[2,4,6];Wang, Hongyi[4];Li, Yangyang[1,5];Zhou, Jiangqi[2,6];Zhang, Liying[1,5];Xiao, Xiao[7];Guo, Yang[4,8]

第一作者：Shi, Liangliang

通信作者：Zhang, LY[1];Guo, Y[2];Xiao, X[3]

机构：[1]Gansu Univ Tradit Chinese Med, Lanzhou, Peoples R China;[2]Tianjin Univ Tradit Chinese Med, Res Ctr Expt Acupuncture Sci, Tianjin, Peoples R China;[3]Baotou Med Coll, Dept Basic & Forens Med, Baotou, Peoples R China;[4]Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, Tianjin, Peoples R China;[5]Key Lab Tradit Chinese Med Explorat & Innovat Tran, Lanzhou, Peoples R China;[6]Tianjin Univ Tradit Chinese Med, Sch Acupuncture & Moxibust & Tuina, Tianjin, Peoples R China;[7]Hubei Univ Chinese Med, Hubei Prov Hosp Tradit Chinese Med, Dept Nephrol, Affiliated Hosp, Wuhan, Peoples R China;[8]Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Lanzhou, Peoples R China;[2]corresponding author), Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, Tianjin, Peoples R China;[3]corresponding author), Hubei Univ Chinese Med, Hubei Prov Hosp Tradit Chinese Med, Dept Nephrol, Affiliated Hosp, Wuhan, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：402

外文期刊名：EXPERIMENTAL NEUROLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001758556900001)】；

基金：This work was supported by the Open Research Project of the National Clinical Research Center for Acupuncture and Moxibustion of Traditional Chinese Medicine (Grant No. NCRCOP2024005) , the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-D-202409) .

语种：英文

外文关键词：TRPV1-tau axis; Alzheimer's disease; Pain sensitization; Bidirectional regulation; Neuroinflammation

摘要：Alzheimer's disease (AD) is a major neurodegenerative disorder characterized by beta-amyloid (A beta) deposition and pathological tau phosphorylation and aggregation, frequently accompanied by chronic pain. Pain sensitization is closely linked to AD progression. Transient receptor potential vanilloid 1 (TRPV1), a key cation channel in pain transduction, is expressed not only in peripheral sensory neurons but also widely in central neurons and glial cells, where it contributes to pain sensitization and neuroinflammation. Emerging evidence indicates a bidirectional regulatory interplay between TRPV1 and tau, forming a "TRPV1-tau axis." This axis acts as a core molecular bridge connecting pain sensitization and AD pathology via calcium dyshomeostasis, mTOR/AMPK, PI3K/Akt/GSK3 beta, and neuroinflammatory pathways. TRPV1 overactivation promotes tau hyperphosphorylation and aggregation through calcium-dependent kinases, metabolic dysregulation, and inflammatory signaling. Conversely, pathological tau modulates TRPV1 expression and function via transcriptional regulation, protein interactions, and impaired axonal transport, establishing a deleterious feedback cycle. Therapeutic interventions targeting this axis, including TRPV1 modulators, tau-directed agents, anti-inflammatory drugs, and natural compounds, demonstrate potential in alleviating both pain sensitivity and cognitive deficits through multi-target mechanisms. However, clinical translation remains challenging due to issues including blood-brain barrier penetration, target selectivity, and a lack of reliable biomarkers. This review systematically outlines the