文献类型：期刊文献

英文题名：RIN1 inhibited TRPV1-dependent pain sensitization in a mouse model of bone cancer pain

作者：Zhang, Yue[1,2,3];Jiang, Hai-Feng[1,2,4];Guo, Ya-Ni[1,2];Wang, Shao-Shan[1,2];Zeng, Xiang-Ru[5];Wang, Kang-Li[5];Wei, Chao-Jun[2,6];Hu, Xiao-Dong[5]

第一作者：张玉娥;Zhang, Yue;张悦

通信作者：Wei, CJ[1];Hu, XD[2]

机构：[1]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China;[2]NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[3]Linyi Cent Hosp, Clin Lab, Linyi, Shandong, Peoples R China;[4]Qingdao Eighth Peoples Hosp, Clin Lab, Qingdao, Shandong, Peoples R China;[5]Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China;[6]Gansu Prov Hosp, Inst Clin Res & Translat Med, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学公共卫生学院

通信机构：[1]corresponding author), NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China.

年份：2026

卷号：22

外文期刊名：MOLECULAR PAIN

收录：;Scopus(收录号：2-s2.0-105044344744);WOS:【SCI-EXPANDED(收录号:WOS:001813362200001)】；

基金：The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (81973296), the fundamental research funds for the central universities (lzujbky-2022-sp09), the Research Project of Gansu Provincial Hospital (22GSSYD-57), the NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor of Gansu Provincial Hospital (23GSSYA-14) and School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University 730000, the Key R&D Program of the Gansu Province Science and Technology Program (24YFFA031).

语种：英文

外文关键词：Ras and Rab interactor 1; transient receptor potential vanilloid 1; bone cancer pain; dorsal root ganglia

摘要：The Ras and Rab interactor 1 (RIN1) is a multifunctional signaling protein that has been implicated in the regulation of tumor cell migration and proliferation. Here we found that RIN1 was abundant in the dorsal root ganglia (DRG) neurons positive for transient receptor potential vanilloid 1 (TRPV1), a critical mediator of pain sensitization in patients with metastatic bone cancer. Our data showed that RIN1 interacted with TRPV1 and induced the endocytosis of TRPV1 through its guanine nucleotide exchange factor activity toward small GTPase Ras-related protein 5 (Rab5). This process limited the duration and magnitude of TRPV1-dependent acute pain responses in intact male mice. Conditioned knockout of RIN1 in the DRG neurons enhanced TRPV1 activity and led to the reflexive nociceptive sensitization and aversive pain behaviors. In mice with the bone cancer pain, we found a significant reduction of RIN1 protein level in the DRG neurons, which correlated with TRPV1 accumulation on the plasma membrane. Special rescue of RIN1 expression in the DRG neurons repressed the surface TRPV1 distribution and alleviated both the reflexive-defensive and affective-motivational aspects of bone cancer pain. Our data thus revealed an important role of RIN1 in the negative control over TRPV1-dependent pain behaviors.