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CX3CR1介导切口术后的机械痛敏：针药复合麻醉的作用

李超, 毛威, 黄云柯, 赵志奇, 吕宁^*

复旦大学脑科学研究院，医学神经生物国家重点实验室，上海 200032

摘要

术后痛是临床中最常见和最需要紧急处理的疼痛，它阻碍患者康复，且容易引起术后并发症。针药复合麻醉是传统针刺和现代麻醉技术相结合的新麻醉方法，即药物全身麻醉的同时在穴位施加针刺，可加强镇痛效果，减少术后痛的发生，但其作用机制尚不明确。趋化因子受体CX3CR1参与多种病理性疼痛的发生和发展，本研究旨在探索CX3CR1是否参与针药复合麻醉的术后镇痛机制。建立C57BL/6J小鼠足趾切口痛模型，用行为学测试检测小鼠痛阈，用免疫组织化学法和Western blot检测脊髓CX3CR1的蛋白表达。结果显示，小鼠足跖切口引起明显的机械触诱发痛和热痛觉过敏。针药复合麻醉明显抑制机械触诱发痛，但对热痛觉过敏没有影响。CX3CR1主要表达于脊髓背角小胶质细胞中，其蛋白水平在足跖切口术后3 d显著升高，针药复合麻醉对CX3CR1蛋白表达水平未见显著影响。CX3CR1基因敲除小鼠足跖切口术后3 d机械痛阈较野生型C57BL/6J小鼠明显升高，但针药复合麻醉的镇痛作用消失；小鼠鞘内注射CX3CR1中和抗体同样可翻转针药复合麻醉的术后镇痛作用。以上结果提示，脊髓小胶质细胞中的CX3CR1参与足跖切口痛和针药复合麻醉术后镇痛作用。

关键词： 手术切口痛; 针药复合麻醉; CX3CR1受体; 小胶质细胞; 脊髓

分类号：Q42;R338

Roles of CX3CR1 in mediation of post-incision induced mechanical pain hypersensitivity: Effects of acupuncture-combined anesthesia

LI Chao, MAO Wei, HUANG Yun-Ke, ZHAO Zhi-Qi, LYU Ning^*

Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

Abstract

Post-incision pain often occurs after surgery and is emergent to be treated in clinic. It hinders the rehabilitation of patients and easily leads to various types of postoperative complications. Acupuncture-combined anesthesia (ACA) is the combination of traditional acupuncture and modern anesthesia, which means acupuncture is applied at acupoints with general anesthesia. It was testified that ACA strengthened the analgesic effect and reduced the occurrence of postoperative pain, but its mechanism was not clear. Numerous reports have shown that chemokine receptor CX3CR1 is involved in the development and progression of many pathological pains. The present study was aimed to reveal whether ACA played the analgesic roles in the post-incision pain by affecting CX3CR1. A model of toe incision pain was established in C57BL/6J mice. The pain threshold was detected by behavioral test, and the expression of CX3CR1 protein was detected by immunohistochemical method and Western blot. The results showed that the significant mechanical allodynia and thermal hyperalgesia were induced by paw incision in the mice. Mechanical allodynia was significantly suppressed by ACA, but thermal hyperalgesia was not changed. CX3CR1 was mainly expressed in microglia in the spinal cord dorsal horn, and its protein level was significantly increased at 3 d after incision compared with that of naïve C57BL/6J mice. ACA did not affect CX3CR1 protein expression at 3 d after incision in the toe incision model mice. Paw withdrawal threshold was significantly increased at 3 d after incision in CX3CR1 knockout (KO) mice compared with that in the C57BL/6J mice. But the analgesic effect of ACA was disappeared in CX3CR1 KO mice. Accordingly, it was also blocked when neutralizing antibody of CX3CR1 was intrathecally injected (i.t.) 1 h before ACA in the C57BL/6J mice. These results suggest that CX3CR1 in microglia is involved in post-incision pain and analgesia of ACA.

Key words: post-incision pain; acupuncture-combined anesthesia; CX3CR1 receptor; microglia; spinal cord

收稿日期：2017-10-24　　录用日期：2017-11-13

通讯作者：吕宁　　E-mail: ninglu@fudan.edu.cn

DOI: 10.13294/j.aps.2018.0035

引用本文：

李超, 毛威, 黄云柯, 赵志奇, 吕宁. CX3CR1介导切口术后的机械痛敏：针药复合麻醉的作用[J]. 生理学报 2018; 70 (3): 237-244.

LI Chao, MAO Wei, HUANG Yun-Ke, ZHAO Zhi-Qi, LYU Ning. Roles of CX3CR1 in mediation of post-incision induced mechanical pain hypersensitivity: Effects of acupuncture-combined anesthesia. Acta Physiol Sin 2018; 70 (3): 237-244 (in Chinese with English abstract).