Microglial depletion under thalamic hemorrhage ameliorates mechanical allodynia and suppresses aberrant axonal sprouting
Microglial depletion under thalamic hemorrhage ameliorates mechanical allodynia and suppresses aberrant axonal sprouting
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DOI：
10.1172/jci.insight.131801
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发表时间：
2020-02-13
期刊：
影响因子：
8
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
--
作者：
Hiraga, Shin-ichiro;Itokazu, Takahide;Yamashita, Toshihide
中枢性中风后疼痛（CPSP）是中风后可能发生的涉及体感系统的神经性疼痛综合征之一。然而，CPSP 的潜在机制仍然很大程度上未知。在这里，我们通过诱导丘脑腹基底复合体局灶性出血建立了 CPSP 小鼠模型，并证实了机械性异常性疼痛的发生。在该模型中，在体感皮层以及受伤的丘脑中观察到小胶质细胞激活。通过使用 CSF1 受体抑制剂，我们发现小胶质细胞耗竭可有效预防 CPSP 模型中异常性疼痛的发生。在异常性疼痛发展的关键阶段，体感皮层中c-fos阳性神经元增加，并伴有丘脑皮质投射的异位轴突萌芽。此外，小胶质细胞消融减弱了体感皮层神经元的过度活跃和回路重组。这些发现表明，小胶质细胞通过促进感觉回路重组，在 CPSP 病理生理学的发展中发挥着至关重要的作用。
Central poststroke pain (CPSP) is one of the neuropathic pain syndromes that can occur following stroke involving the somatosensory system. However, the underlying mechanism of CPSP remains largely unknown. Here, we established a CPSP mouse model by inducing a focal hemorrhage in the thalamic ventrobasal complex and confirmed the development of mechanical allodynia. In this model, microglial activation was observed in the somatosensory cortex, as well as in the injured thalamus. By using a CSF1 receptor inhibitor, we showed that microglial depletion effectively prevented allodynia development in our CPSP model. In the critical phase of allodynia development, c-fos-positive neurons increased in the somatosensory cortex, accompanied by ectopic axonal sprouting of the thalamocortical projection. Furthermore, microglial ablation attenuated both neuronal hyperactivity in the somatosensory cortex and circuit reorganization. These findings suggest that microglia play a crucial role in the development of CPSP pathophysiology by promoting sensory circuit reorganization.