A Role for Transmembrane Protein 16C/Slack Impairment in Excitatory Nociceptive Synaptic Plasticity in the Pathogenesis of Remifentanil-induced Hyperalgesia in Rats  

作　　者：Yize Li Linlin Zhang Jing Li Chunyan Wang Yi Chen Yuan Yuan Keliang Xie Guolin Wang Yonghao Yu 

机构地区：[1]Department of Anesthesiology,Tianjin Medical University General Hospital,Tianjin Research Institute of Anesthesiology,Tianjin 300052,China

出　　处：《Neuroscience Bulletin》2021年第5期669-683,共15页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (82071243, 81801107, 81772043, and 81400908);Tianjin Natural Science Foundation (20JCYBJC00460);Young Elite Scientists Sponsorship Program by Tianjin Municipality, China (TJSQNTJ-2020-10)。

摘　　要：Remifentanil is widely used to control intraoperative pain. However, its analgesic effect is limited by the generation of postoperative hyperalgesia. In this study, we investigated whether the impairment of transmembrane protein 16C(TMEM16C)/Slack is required for a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor(AMPAR) activation in remifentanil-induced postoperative hyperalgesia. Remifentanil anesthesia reduced the paw withdrawal threshold from 2 h to 48 h postoperatively,with a decrease in the expression of TMEM16C and Slack in the dorsal root ganglia(DRG) and spinal cord.Knockdown of TMEM16C in the DRG reduced the expression of Slack and elevated the basal peripheral sensitivity and AMPAR expression and function. Overexpression of TMEM16C in the DRG impaired remifentanilinduced ERK1/2 phosphorylation and behavioral hyperalgesia. AMPAR-mediated current and neuronal excitability were downregulated by TMEM16C overexpression in the spinal cord. Taken together, these findings suggest that TMEM16C/Slack regulation of excitatory synaptic plasticity via GluA1-containing AMPARs is critical in the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats.

关 键 词：Transmembrane protein 16C Opioid-induced hyperalgesia A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Slack channel Synaptic plasticity 

分 类 号：R965[医药卫生—药理学]