Physiology, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland.
Physiology, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, University Road, Galway, Ireland.
Brain Behav Immun. 2014 Nov;42:147-56. doi: 10.1016/j.bbi.2014.06.015. Epub 2014 Jun 30.
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 2week 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-1β, 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-1β, 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.
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关联中的作用，数据很少。本研究检查了小胶质细胞抑制剂米诺环素对抑郁样行为、脊髓神经结扎（SNL）引起的机械性和冷感觉异常以及前额叶皮质中编码小胶质细胞标志物（M1 与 M2 极化）和炎症介质的基因表达变化的影响在嗅球切除术（OB）大鼠抑郁模型中。急性米诺环素给药不会改变 OB 诱导的抑郁样行为，但可预防 OB 和假手术大鼠的 SNL 诱导的机械性痛觉过敏。相比之下，慢性米诺环素可减轻 OB 诱导的抑郁样行为，并可预防 SNL 诱导的机械性痛觉过敏在 OB 大鼠中，但在假手术大鼠中没有。进一步分析表明，慢性米诺环素可减轻 OB 大鼠的 SNL 诱导的机械性痛觉过敏，在 2 周的测试期间几乎所有时间点都有这种作用，而在假手术大鼠中仅从 SNL 后第 10 天开始观察到这种作用。慢性米诺环素给药可降低假手术 SNL 动物前额叶皮质中 CD11b（小胶质细胞激活的标志物）和促炎细胞因子 IL-1β 的表达。相比之下，M2 小胶质细胞标志物（MRC2）和抗炎细胞因子 IL-10 的表达增加，以及 IL-1β、IL-6 和 SOCS3 在 OB-SNL 动物的前额叶皮质中表达增加，在慢性米诺环素给药后。因此，慢性米诺环素可减轻神经病理性疼痛行为，并调节小胶质细胞激活和炎症介质的中枢表达，其方式取决于是否存在抑郁样表型。
