凝血酶敏感蛋白2通过介导小鼠初级感觉神经元中Nav 1.7膜锚定促进神经病理性疼痛
凝血酶敏感蛋白2通过介导小鼠初级感觉神经元中Nav1.7膜锚定促进神经病理性疼痛
作者： 小柯机器人 发布时间：2026/11/12 10:28:49
本期文章：《神经科学通报》：Online/在线发表
西安交通大学梁玲利研究组发现了血栓反应蛋白2通过介导小鼠初级感觉神经元Nav1.7膜锚定促进神经性疼痛。相关论文于2026年11月5日发表于国际顶尖学术期刊《神经科学通报》杂志上。
凝血酶敏感蛋白2（TSP2）是凝血酶敏感蛋白家族细胞外基质蛋白的成员，介导关键的细胞-细胞和细胞-基质相互作用。然而，其在神经病理性疼痛中的潜在作用仍不清楚。研究人员证明，TSP2特异性表达于异凝集素B4阴性的背根神经节（DRG）神经元中。在腰4（L4）脊神经结扎（SNL）后，TSP2表达在损伤（L4）和未损伤（L3）的DRG中均上调。值得注意的是，siRNA介导的TSP2敲低减弱了SNL诱导的痛觉过敏，且作用于神经病理性疼痛的发展期，而非维持期。相反，仅在DRG中神经元特异性过表达TSP2就足以产生增强的伤害性行为。机制上，SNL增强了TSP2与Nav1.7之间的相互作用，促进L3和L4 DRG中Nav1.7的膜锚定，从而增加DRG神经元兴奋性。这些发现确立了TSP2作为一种新的Nav1.7相互作用蛋白，以及预防慢性神经病理性疼痛的潜在治疗靶点。
附：英文原文
Title: Thrombospondin 2 Promotes Neuropathic Pain by Mediating Nav1.7 Membrane Anchoring in Mouse Primary Sensory Neurons
Author: Wei, Jianxiong, Wang, Yuying, Zhao, Zhi-Xia, Chen, Hongxiu, Chang, Shuyang, Yang, Qianwen, Wang, Huan, Liu, Xinqi, Zhou, Xiaoqiong, Li, Xu-Hui, Zhang, Jun, Liang, Lingli
Issue&Volume: 2026-11-05
Abstract: Thrombospondin 2 (TSP2), a member of the thrombospondin family of extracellular matrix proteins, mediates critical cell-cell and cell-matrix interactions. However, its potential roles in neuropathic pain remain unclear. We demonstrate that TSP2 is specifically expressed in isolectin B4-negative dorsal root ganglion (DRG) neurons. Following lumbar 4 (L4) spinal nerve ligation (SNL), TSP2 expression was upregulated in both injured (L4) and uninjured (L3) DRGs. Notably, siRNA-mediated TSP2 knockdown attenuated SNL-induced pain hypersensitivity during the development phase, but not during the maintenance phase, of neuropathic pain. Conversely, neuron-specific TSP2 overexpression in the DRG alone was sufficient to produce enhanced nociceptive behavior. Mechanistically, SNL enhanced the interaction between TSP2 and Nav1.7, promoting Nav1.7 membrane anchoring in the L3 and L4 DRGs and thereby increasing DRG neuronal excitability. These findings establish TSP2 as a novel Nav1.7-interacting protein and a potential therapeutic target for preventing chronic neuropathic pain.
DOI: 10.1007/s12264-026-01737-9
Source: https://link.springer.com/article/10.1007/s12264-026-01737-9