Inflammation Confers Dual Effects on Nociceptive Processing in Chronic Neuropathic Pain Model
Inflammation Confers Dual Effects on Nociceptive Processing in Chronic Neuropathic Pain Model
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DOI：
10.1097/aln.0b013e31820b8b1e
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发表时间：
2011-03-01
期刊：
影响因子：
8.8
通讯作者：
Day, Yuan-Ji
中科院分区：
文献类型：
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作者：
Liou, Jiin-Tarng;Liu, Fu-Chao;Day, Yuan-Ji
背景：虽然炎症会引起疼痛，但免疫细胞也会产生可以有效抵消疼痛的介质。为了进一步阐明免疫反应的作用，我们对不同免疫功能低下水平的小鼠进行部分坐骨神经结扎，分析了疼痛行为、几种炎症信号和阿片类肽的关系。方法：部分结扎C57BL/6C、非肥胖糖尿病（NOD）或非肥胖糖尿病-严重联合免疫缺陷（NOD-SCID）小鼠的坐骨神经。观察对机械和辐射热刺激的反应。通过免疫组织化学和流式细胞术检测炎症。使用实时聚合酶链反应和酶联免疫吸附测定或免疫染色分析炎症细胞因子和阿片肽。结果：与 C57BL/6C 小鼠相比，免疫功能低下小鼠的炎症程度较轻。此外，免疫功能低下的小鼠在早期阶段的疼痛过敏程度较低。而促炎性肿瘤坏死因子-α (TNF-α)、白细胞介素 1 β (IL-1 β)、白细胞介素 6 (IL-6) 和干扰素 γ (IFN-γ) 以及抗炎白细胞介素 1 受体拮抗剂 (IL-1Ra)、白细胞介素 4 (IL-4)、白细胞介素 10 (IL-10) 和白细胞介素 13 (IL-13) 细胞因子表达和蛋白质增加在 C57BL/6C 小鼠中，它们在免疫功能低下的小鼠中较低。尽管 C57BL/6C 小鼠中脑啡肽、强啡肽和 β-内啡肽信使 RNA 表达也有所增加，并在第 14 天达到峰值，但在免疫功能低下的小鼠中并未观察到这一结果。 结论：炎症对神经损伤的影响与双相调节很复杂。在早期阶段，多种促炎细胞因子被释放，导致疼痛加剧。相比之下，阿片肽和抗炎细胞因子的镇痛作用在损伤后期更占主导地位，导致疼痛反应减弱。
Background: Although inflammation induces pain, immune cells also produce mediators that can effectively counteract it. To further elucidate the role of the immune response, we analyzed the relationship of pain behavior, several inflammatory signals, and opioid peptides using partial sciatic nerve ligation in mice at different levels of immunocompromise.Methods: Sciatic nerves of C57BL/6C, nonobese diabetic (NOD), or nonobese diabetic-severe combined immune deficiency (NOD-SCID) mice were partially ligated. Responses to mechanical and radiant heat stimuli were observed. Inflammation was detected by immunohistochemistry and flow cytometry. Inflammatory cytokines and opioid peptides were analyzed using real-time polymerase chain reaction and enzyme-linked immunosorbent assay or immunostaining.Results: Inflammation in immunocompromised mice was subordinate when compared with that seen in C57BL/6C mice. In addition, immunocompromised mice had less pain hypersensitivity at early stages. Whereas proinflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma), as well as antiinflammatory interleukin 1 receptor antagonist (IL-1Ra), interleukin 4 (IL-4), interleukin 10 (IL-10), and interleukin 13 (IL-13) cytokine expression and protein were increased in C57BL/6C mice, they were lower in immunocompromised mice. Although enkephalin, dynorphin, and beta-endorphin messenger RNA expression also increased in C57BL/6C mice, peaking on day 14, this result was not observed in immunocompromised mice.Conclusion: The contribution of inflammation to nerve injury is complex with biphasic modulation. During the early phase, a wide range of proinflammatory cytokines are released, leading to enhanced pain. In contrast, the analgesic effect of opioid peptides and antiinflammatory cytokines was more predominate in the later phases of injury, leading to attenuated pain responses.