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

• 影响指数: 5.271
• 发表时间: May 2021
• 来源期刊: Neurosci Bull
• DOI: 10.1007/s12264-021-00652-5
• PMID: 33779892
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Li Y,Zhang L,Li J,Wang C,Chen Y,Yuan Y,Xie K,Wang G,Yu Y

关键词: Opioid-induced hyperalgesia; Slack channel; Synaptic plasticity; Transmembrane protein 16C; Α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

Mesh: Animals; Hyperalgesia / chemically induced; Neuronal Plasticity; Nociception; Rats; Rats, Sprague-Dawley; Remifentanil / toxicity

Abstract

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 α-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 remifentanil-induced 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.