Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain
Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain
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DOI：
10.1016/j.neuron.2021.11.020
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发表时间：
2022-02-16
期刊：
影响因子：
16.2
通讯作者：
Eijkelkamp，Niels
中科院分区：
文献类型：
--
作者：
van der Vlist，Michiel;Raoof，Ramin;Eijkelkamp，Niels
目前的范式是炎症性疼痛在炎症停止后被动消退。然而，在相当大比例的炎性疾病患者中，炎症的消退不足以消除疼痛，导致慢性疼痛。缺乏对炎症性疼痛如何解决的机制性见解。在这里，我们表明，巨噬细胞主动控制炎症疼痛的分辨率远程从炎症部位的线粒体转移到感觉神经元。在小鼠炎性疼痛消退期间，M2样巨噬细胞浸润包含感觉神经元胞体的背根神经节，同时感觉神经元中氧化磷酸化恢复。疼痛的缓解和线粒体的转移需要巨噬细胞上的CD200受体（CD200 R）和感觉神经元上的非经典CD200 R配体iSec1的表达。我们的数据揭示了一个新的机制，积极解决炎症性疼痛。
The current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight into how inflammatory pain is resolved is lacking. Here, we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.