文献类型：期刊文献

英文题名：Advanced glycation end products mediated diabetic neuropathic pain via activation protein tyrosine phosphatase 1B in the spinal cord dorsal horn

作者：Wang, Jing[1,2];Li, Xiao-Qin[1,2];Sun, Rui-Li[1,2];Yang, Yu-Hang[3,4];Li, Wen-Jing[3,4];Shen, Yi-Ke[2];Wang, Jia-Jia[2];Zhang, Zhi-Xian[2];Yang, Qing-Shan[3];Wu, Shu-Jin[2]

第一作者：Wang, Jing

通信作者：Wu, SJ[1];Yang, QS[2]

机构：[1]Ningxia Med Univ, Sch Pharm, Yinchuan, Ningxia, Peoples R China;[2]Gansu Prov Hosp, Dept Pharm, 196 East Gang Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Prov Hosp, Dept Orthoped, 196 East Gang Rd, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China

第一机构：Ningxia Med Univ, Sch Pharm, Yinchuan, Ningxia, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Pharm, 196 East Gang Rd, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Prov Hosp, Dept Orthoped, 196 East Gang Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2025

外文期刊名：DIABETIC MEDICINE

收录：;Scopus(收录号：2-s2.0-105016704050);WOS:【SCI-EXPANDED(收录号:WOS:001573552800001)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 82060409 and 82460427; Gansu Natural Science Foundation, Grant/Award Number: 23JRRA1771; Gansu Provincial Health Science and Technology Research, Grant/Award Number: GSWSQN2022- 07; Youth Talent Project of Gansu Province, Grant/Award Number: 2025QNGR67; Science and Technology Plan Project of Lanzhou, Grant/Award Number: 2023-4-59

语种：英文

外文关键词：advanced glycation end products; diabetic neuropathic pain; N-methyl-D-aspartate receptor; protein tyrosine phosphatase 1B

摘要：Aims Diabetic neuropathic pain (DNP) is a debilitating complication of diabetes mellitus that significantly impairs patients' quality of life. In this study, we aimed to investigate whether much higher plasma advanced glycation end products (AGEs) concentrations discriminate between diabetes-affected individuals with pain and those without pain.Methods We administered exogenous AGEs intravenously to C57BL/6J wild-type mice and assessed nociceptive behaviours, as well as anxiety- and depression-like behaviours. To explore the further mechanism, we knocked out the protein tyrosine phosphatase 1B (PTP1B) in the spinal dorsal horn by injecting the AAV viral construct encoding short-hairpin RNA (shRNA). Electrophysiological recordings were used to assay the N-methyl-D-aspartate receptor (NMDAR) function.Results Our results demonstrated that elevated plasma AGEs levels led to significant hyperalgesia, which was alleviated by the specific knockout of PTP1B in the spinal dorsal horn. However, this knockout did not ameliorate AGEs-induced anxiety- and depression-like behaviours. Electrophysiological recordings revealed that AGEs enhanced NMDAR-mediated excitatory postsynaptic currents (eEPSCs) in spinal cord slices, an effect attenuated by PTP1B inhibition. Biochemical analyses showed that AGEs decreased phosphorylation at the Tyr529 site of Src kinase and increased phosphorylation at the Tyr1472 site of the NMDAR subunit 2B (GluN2B); these changes were reversed by PTP1B knockdown.Conclusion These findings suggest that elevated plasma AGEs contribute to hyperalgesia through a PTP1B-dependent mechanism involving Src/NMDAR signalling in the spinal dorsal horn. Targeting the AGEs-PTP1B-NMDAR pathway may offer new therapeutic strategies for managing DNP.