Shi Changxi, Liu Yue, Zhang Wei, Lei Yishan, Lu Cui'e, Sun Rao, Sun Yu'e, Jiang Ming, Gu Xiaoping, Ma Zhengliang
1 Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province, China.
2 Department of Anesthesiology, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province, China.
Mol Pain. 2017 Jan-Dec;13:1744806917725636. doi: 10.1177/1744806917725636.
Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases.
越来越多的研究表明，瑞芬太尼作为临床麻醉中广泛使用的阿片类镇痛药，可激活伤害感受系统并加重术后疼痛。胶质细胞被认为与瑞芬太尼诱导的痛觉过敏有关。电针是一种用于缓解各种疼痛状况且副作用较少的辅助治疗方法，胶质细胞可能参与其镇痛作用。在本研究中，我们探究了术中电针是否可通过抑制脊髓胶质细胞的激活、脊髓促炎细胞因子的产生以及脊髓丝裂原活化蛋白激酶的激活来缓解瑞芬太尼诱导的术后痛觉过敏。
本研究采用瑞芬太尼诱导的大鼠术后痛觉过敏模型。手术期间在双侧足三里（ST36）穴位进行电针治疗。在不同时间点进行行为学测试，包括机械性异常疼痛和热痛觉过敏测试。通过蛋白质免疫印迹法和/或免疫荧光法检测脊髓中星形胶质细胞标志物胶质纤维酸性蛋白、小胶质细胞标志物离子钙结合衔接分子1、促炎细胞因子以及磷酸化丝裂原活化蛋白激酶。
手术切口和瑞芬太尼输注均可诱导机械性异常疼痛和热痛觉过敏，且瑞芬太尼输注显著加剧并延长了切口诱导的伤害感受作用。手术切口、瑞芬太尼输注后，尤其是两者联合后，胶质纤维酸性蛋白、离子钙结合衔接分子1、促炎细胞因子（白细胞介素-1β和肿瘤坏死因子-α）以及磷酸化丝裂原活化蛋白激酶（p-p38、p-JNK和p-ERK1/2）均上调。术中电针显著减轻了切口和/或瑞芬太尼诱导的伤害感受作用、脊髓胶质细胞激活、促炎细胞因子上调以及磷酸化丝裂原活化蛋白激酶上调。
我们的研究表明，术中电针可通过抑制脊髓胶质细胞的激活、脊髓促炎细胞因子的上调以及脊髓丝裂原活化蛋白激酶的激活来缓解瑞芬太尼诱导的术后痛觉过敏。
