姜 爽,颜丽晖,夏 蓉,白静慧△

Neuroimmune and inflammation mechanisms of Opioid-induced hyperalgesia

摘要:

目的：阿片所致痛觉敏化的机制尚未明确。作为神经元机制外的重要补充，神经炎症及胶质细胞激活作为阿片类药物诱导的痛觉敏化的重要非神经元机制应该得到更多关注。方法：筛选以胶质细胞激活为载体，Toll样受体及细胞因子、趋化因子变化等免疫炎症介质为研究对象的文献进行综述。结果：不同的研究设计均使用通过重复阿片类药物注射的方法建立痛觉敏化的动物模型，笼统而言，阿片类物质可能通过与μ阿片受体及内源性适应性非特异受体（Toll样受体、ATP受体、趋化因子受体等）激活星形胶质细胞和小胶质细胞内包括NFκB、MAPK、pJNK、ERK等信号级联反应，继而促炎症因子如细胞因子及趋化因子释放，参与并强化了胶质细胞活化状态并诱导感觉神经元的异常兴奋。结论：多数研究结论指向对免疫激活的抑制和炎症反应的阻断会减少痛觉敏化的发生，但仍有部分研究对此提出质疑和校正。因此对阿片所致痛觉敏化的神经免疫机制仍需要更深入细致的探讨。

Abstract:

Objective: The neuroimmune mechanisms of OIH were still largely unknown. Neuroimmune and inflammatory activity as the non-neuronal mechanisms of Opioid-induced hyperalgesia (OIH) deserves more attention. Method: The existing literatures focusing OIH was reviewed, especially the researches on activation of astrocyte and microglia, expression of Toll-like receptors and changes in cytokines and chemokines. Result: Animal models from repeated opioids injection were the most usual designs in these researches. It could be roughly assumed that opioids may bind to μ opioid receptor and other endogenous receptors, then activate signal cascades in astrocyte and microglia, including NF-κB p65, p-JNK, ERK, etc., then pro-inflammatory factors such as cytokines and chemokines release, which may strengthen the activation of glial cells and nociceptive neurons. Conclusion: Most researches demonstrated that blocking activation of astrocyte or microglia could reduce the occurrence of OIH, as well as anti-inflammation agents. But it must be noticed that many factors may affect the research results and the controversies on this topic are still rising. The inflammation and neuroimmune mechanism of OIH still need further researches to improve.