Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats
Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats
复制标题
鞘内注射 KN93 通过抑制大鼠脊髓 CaMKII 磷酸化来减轻瑞芬太尼引起的矛盾术后痛觉过敏
DOI：
10.1016/j.pbb.2015.04.015
复制
发表时间：
2015-07-01
影响因子：
3.6
通讯作者：
Gu, Xiaoping
中科院分区：
文献类型：
--
作者：
Jiang, Ming;Zhang, Wei;Gu, Xiaoping
目的：瑞芬太尼是一种短效、高选择性的MU阿片激动剂，用于许多临床手术中的止痛。在一定条件下，瑞芬太尼可产生“矛盾”的痛觉过敏。本研究旨在探讨这种“悖论”效应的作用机制。方法：将SD大鼠分为6组，分别为对照组和治疗组。测定大鼠的缩足机械阈值和缩足热潜伏期。观察大鼠鞘内注射前24 h、术后2 h、6 h、24 h、48 h的行为学变化。根据疼痛行为指标的变化，分别于术后2、6、24、48h取材。Western blotting检测脊髓背角钙/钙调素依赖性蛋白激酶II(CaMKII)的表达。结果：术中输注瑞芬太尼可诱导大鼠术后痛觉过敏。鞘内注射KN93可剂量依赖地提高小鼠的缩足机械阈值和缩足热潜伏期的痛阈值。Western blotting结果显示，瑞芬太尼可显著提高脊髓背角CaMKII的磷酸化水平。结论：鞘内注射KN93可通过抑制脊髓CaMKII的磷酸化，减轻术中注射瑞芬太尼所致的术后痛敏反应。(C)2015 Elsevier Inc.保留所有权利。
Aims: Remifentanil is a short-acting and highly selective mu opiate agonist that is used in many clinical surgical situations for intraoperative pain relief. Under certain conditions, remifentanil can produce "paradoxical" hyperalgesia. This study aims to investigate mechanisms of actions mediating this "paradoxical" effect.Methods: Sprague Dawley rats were divided into 6 groups including control and treatment groups. The paw withdrawal mechanical threshold and the paw withdrawal thermal latency of the rats were tested. The changes of rat behaviors were measured at 24 h before intrathecal injection and at 2 h, 6 h, 24 h, and 48 h after operation. According to the changes in behavioral indicators of pain, the specimens of all groups were collected at 2 h, 6 h, 24 h, and 48 h after the operation. The level of calcium/calmodulin-dependent protein kinase II (CaMKII) in the spinal dorsal horn was analyzed by Western blotting.Results: Intraoperative infusion of remifentanil induced postoperative hyperalgesia in the rats. Intrathecal KN93 injection increased nociceptive thresholds of paw withdrawal mechanical threshold and paw withdrawal thermal latency in a dose-dependent manner. Western blotting results showed that CaMKII phosphorylation in the spinal dorsal horn was increased significantly by remifentanil. Inhibition of CaMKII phosphorylation relieved the hyperalgesia pain state.Conclusions: Intrathecal injection of KN93 attenuates postoperative hyperalgesia induced by intraoperative infusion of remifentanil in rats through inhibiting spinal CaMKII phosphorylation. (C) 2015 Elsevier Inc. All rights reserved.