文献类型：期刊文献

英文题名：PTP1B in dorsal root ganglion nociceptors drives neuropathic pain via a presynaptic Src/GluN2B signaling pathway

作者：Li, Xiao-Qin[1,2];Wu, Shu-Jin[2];Sun, Rui-Li[1,2];Li, Wen-Jing[3,4];Yang, Yu-Hang[3,4];Liao, Xi-Wu[3,4];Huang, Zi-Yan[3,4];Zhang, Jia-Wei[3,4];Sun, Fan[3,4]

第一作者：Li, Xiao-Qin

通信作者：Wu, SJ[1]

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

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

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Pharm, Lanzhou, Peoples R China.

年份：2026

外文期刊名：REGIONAL ANESTHESIA AND PAIN MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001858087200001)】；

基金：This work was supported by the National Natural Science Foundation of China (grant numbers 82060409, 82460427); the Provincial Natural Science Foundation of Gansu (grant number 23JRRA1771, 23JRRA1773); the Gansu Provincial Health Science and Technology Research (grant number GSWSQN2022-07); Gansu Provincial Hospital Institutional Research Project (24GSSYA-2). State Key Laboratory Project for Neuro-Oncological Drug R&D (grant number SKLSIM-F-2025056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Pain Measurement; Synaptic Transmission; Peripheral Nerve Injuries

摘要：Background Neuropathic pain, a debilitating chronic condition, remains a major clinical challenge due to its complex pathogenesis and limited treatment options. Protein tyrosine phosphatase 1B (PTP1B), a key regulator of tyrosine phosphorylation, has been implicated in various diseases, yet its specific role and mechanism in nociceptive processing within the dorsal root ganglion (DRG) are poorly understood.Methods To investigate this, we used peripheral nerve injury models to assess PTP1B expression in the DRG. We employed nociceptor-specific overexpression and targeted knockdown of PTP1B to evaluate its effect on neuropathic pain-like behaviors, including mechanical allodynia and negative affect. Furthermore, we used electrophysiological recordings of miniature excitatory postsynaptic currents and pharmacological inhibition targeting Src kinase and N-methyl-D-aspartate (NMDA) receptor GluN2B to delineate the underlying molecular mechanisms.Results Peripheral nerve injury induced a sustained upregulation of PTP1B predominantly in non-peptidergic nociceptors of the DRG. Mimicking this upregulation through nociceptor-specific overexpression elicited robust neuropathic pain-like behaviors. Conversely, targeted PTP1B knockdown therapeutically reversed established pain hypersensitivity. Mechanistically, PTP1B interacted with and activated Src kinase by dephosphorylating its inhibitory site at Tyr529. This led to enhanced phosphorylation of the NMDA receptor GluN2B subunit at Tyr1472, increasing presynaptic glutamate release in the spinal dorsal horn, as evidenced by elevated miniature excitatory postsynaptic currents. Consequently, pharmacological inhibition of either GluN2B or Src largely reversed PTP1B-driven pain sensitization.Conclusions Our findings identified PTP1B in DRG nociceptors as a critical upstream regulator of the presynaptic Src/GluN2B pathway, establishing it as a promising therapeutic target for the treatment of neuropathic pain.