Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain. (1st July 2018)

• Record Type: Journal Article
• Authors: Guo, Ruijuan; Li, Huili; Li, Xueyang; Sun, Yuqing; Miao, Huihui; Ma, Danxu; Hong, Fangxiao; Zhang, Ye; Guan, Yun; Li, Junfa; Tian, Ming; Wang, Yun
• Is Part Of: Neuroscience. Volume 382(2018)
• Page Start: 14
• Page End: 22
• Publication Date: 2018-07-01
• Subjects: AMPA α-amino-3-hydroxy-5-methyl-4-isoxazole propionate -- CPS cumulative pain score -- PSD-95 postsynaptic density protein 95 -- PWT paw withdrawal threshold -- siRNA small interfering ribonucleic acid -- TTBS Tween/Tris-buffered saline solution; postoperative pain -- spinal cord -- neuroligin 2 -- AMPA receptor -- GluR1 -- PSD-95; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.04.028
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Plantar incision increases the expression of neuroligin 2 and GluR1 in postsynaptic membrane. The interaction between neuroligin 2 and PSD-95 is enhanced after plantar incision. Pretreatment with intrathecal neuroligin 2 siRNA attenuates postoperative pain in rats. Abstract: 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.