Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain
Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain
复制标题
脊髓背角突触后膜中 Neuroligin 2 水平的增加可能导致术后疼痛
DOI：
10.1016/j.neuroscience.2018.04.028
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发表时间：
2018-07-01
期刊：
影响因子：
3.3
通讯作者：
Wang, Yun
中科院分区：
文献类型：
--
作者：
Guo, Ruijuan;Li, Huili;Wang, Yun
神经连接素2是一种突触细胞黏附分子，主要分布在抑制性突触中，通过蛋白质间的相互作用对突触功能的调节起着至关重要的作用。然而，研究人员还没有明确确定神经连接蛋白2是否参与了术后疼痛的发生。本研究采用免疫印迹、免疫荧光染色和免疫共沉淀等方法研究了神经连接素2在术后疼痛超敏反应中的重要作用。以小分子干扰核糖核酸(SiRNA)为靶点的神经连接蛋白2抑制神经连接蛋白2的表达。我们的研究发现，足底切开导致了术后疼痛超敏反应，其特征表现为缩足阈值和累积疼痛评分。足底切开后3h和1d，观察到同侧脊髓背角突触后膜神经连接素2和GluR1的表达上调。此外，在足底切开后3h，与神经连接素2抗体共沉淀的PSD-95在同侧背角的数量明显高于对照组。鞘内注射siRNA靶向神经连接素2以减少脊髓神经连接素2的表达，可明显抑制同侧背角GluR1的痛敏反应和减少突触靶向性。我们的研究表明，神经连接素2和PSD-95之间的相互作用以及随后GluR1在同侧背角的突触靶向参与了术后疼痛超敏反应。(C)2018年IBRO。爱思唯尔有限公司出版。保留所有权利。
Neuroligin 2 is a synaptic cell adhesion molecule that is mainly located in inhibitory synapses and is crucial in the regulation of synapse function through protein-protein interactions. However, researchers have not clearly determined whether neuroligin 2 is involved in the development of postoperative pain. In the current study, Western blot, immunofluorescence staining and co-immunoprecipitation were used to examine the critical role of neuroligin 2 in postoperative pain hypersensitivity. A small interfering ribonucleic acid (siRNA)-targeting neuroligin 2 was used to inhibit neuroligin 2 expression. Our data found that plantar incision induced postoperative pain hypersensitivity, which was characterized by paw withdrawal threshold and cumulative pain score. The upregulation of neuroligin 2 and GluR1 expression in the postsynaptic membranes of ipsilateral spinal dorsal horn was observed at 3 h and 1 day after plantar incision. Additionally, at 3 h after plantar incision, the amount of PSD-95 that was co-immunoprecipitated with neuroligin 2 antibody was significantly increased in the ipsilateral dorsal horn, as compared to that of the control group. Intrathecal pretreatment of siRNA-targeting neuroligin 2 to reduce the neuroligin 2 expression in the spinal cord significantly inhibited the pain hypersensitivity and reduced the synaptic targeting of GluR1 in ipsilateral dorsal horns. Our study indicates that the incision-induced interaction between neuroligin 2 and PSD-95 and subsequent synaptic targeting of GluR1 in ipsilateral dorsal horns contribute to postoperative pain hypersensitivity. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.