Minocycline modulates neuropathic pain behaviour and cortical M1-M2 microglial gene expression in a rat model of depression
Minocycline modulates neuropathic pain behaviour and cortical M1-M2 microglial gene expression in a rat model of depression
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DOI：
10.1016/j.bbi.2014.06.015
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发表时间：
2014-11-01
影响因子：
15.1
通讯作者：
Roche, Michelle
中科院分区：
文献类型：
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作者：
Burke, Nikita N.;Kerr, Daniel M.;Roche, Michelle
关于小胶质细胞和神经炎症过程在慢性疼痛和抑郁之间的联系方面的数据很少。本研究观察了小胶质细胞抑制剂米诺环素对嗅球切除(OB)抑郁症模型大鼠抑郁样行为、脊神经结扎(SNL)诱导的机械性和冷性超敏以及小胶质细胞标志物(M1与M2极化)编码基因和前额叶皮质炎症介质基因表达的相关变化的影响。二甲胺四环素急性给药不能改变OB诱导的抑郁样行为，但能预防SNL诱导的机械痛觉异常。相比之下，慢性米诺环素可减轻OB诱导的抑郁样行为，并防止SNL诱导的OB大鼠机械性超敏的发展，但不能阻止假手术。进一步的分析表明，在2周的测试期间，慢性米诺环素几乎在所有时间点都能减轻SNL诱导的OB大鼠的机械性痛觉异常，而这种作用仅在SNL后第10天观察到。慢性给予米诺环素降低了小胶质细胞激活的标志物CD11b和M1促炎细胞因子IL-1β在假SNL动物前额叶皮质的表达。与之相比，慢性米诺环素后OB-SNL动物前额叶皮质M2小胶质细胞标志物(MRC2)和抗炎细胞因子IL-10表达增加，IL-1β、IL-6和SOCS3表达增加。因此，慢性米诺环素可减轻神经病理性疼痛行为，并调节小胶质细胞的激活和炎症介质的中枢表达，其方式取决于抑郁样表型的存在与否。(C)2014 Elsevier Inc.保留所有权利。
There is a paucity of data on the role of microglia and neuroinflammatory processes in the association between chronic pain and depression. The current study examined the effect of the microglial inhibitor minocycline on depressive-like behaviour, spinal nerve ligation (SNL)-induced mechanical and cold allodynia and associated changes in the expression of genes encoding microglial markers (M1 vs. M2 polarisation) and inflammatory mediators in the prefrontal cortex in the olfactory bulbectomised (OB) rat model of depression. Acute minocycline administration did not alter OB-induced depressive-like behaviour but prevented SNL-induced mechanical allodynia in both OB and sham rats. In comparison, chronic minocycline attenuated OB-induced depressive-like behaviour and prevented the development of SNL-induced mechanical allodynia in OB, but not sham, rats. Further analysis revealed that SNL-induced mechanical allodynia in OB rats was attenuated by chronic minocycline at almost all time-points over a 2 week testing period, an effect observed only from day 10 post-SNL in sham rats. Chronic administration of minocycline reduced the expression of CD11b, a marker of microglial activation, and the M1 pro-inflammatory cytokine IL-1 beta, in the prefrontal cortex of sham-SNL animals. In comparison, the expression of the M2 microglia marker (MRC2) and anti-inflammatory cytokine IL-10 was increased, as were IL-1 beta, IL-6 and SOCS3, in the prefrontal cortex of OB-SNL animals following chronic minocycline. Thus, chronic minocycline attenuates neuropathic pain behaviour and modulates microglial activation and the central expression of inflammatory mediators in a manner dependent on the presence or absence of a depressive-like phenotype. (C) 2014 Elsevier Inc. All rights reserved.