Nerve Injury-Activated Microglia Engulf Myelinated Axons in a P2Y12 Signaling-Dependent Manner in the Dorsal Horn
Nerve Injury-Activated Microglia Engulf Myelinated Axons in a P2Y12 Signaling-Dependent Manner in the Dorsal Horn
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DOI：
10.1002/glia.21053
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发表时间：
2010-11-15
期刊：
影响因子：
6.2
通讯作者：
Kiyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Maeda, Mitsuyo;Tsuda, Makoto;Kiyama, Hiroshi
神经病理性疼痛的潜在机制知之甚少。然而，一些研究暗示了位于背角的反应性小胶质细胞在神经病理性疼痛中的作用。为了阐明激活的小胶质细胞在神经病理性疼痛中的作用，我们使用电子显微镜研究了小胶质细胞和背角中其他神经成分之间的相互作用。小胶质细胞更丰富地定位在第二-第三层的背角比其他地区，其中一些人坚持和吞噬受伤和未受伤的有髓轴突。这种小胶质细胞吞噬在正常背角中很少观察到，并且在手术侧上，术后第7天，附着于有髓轴突的小胶质细胞的数量显著增加。然而，通过鞘内注射其拮抗剂AR-C69931 MX来阻断小胶质细胞中的P2 Y12 ATP受体后，附着在有髓鞘轴突上的小胶质细胞数量的增加以及触觉异常性疼痛的发生明显受到抑制，尽管激活的小胶质细胞的数量没有显着变化。这些结果表明，在背角中通过P2 Y12信号转导被激活的小胶质细胞吞噬有髓鞘轴突可能是神经病理性疼痛发病机制中的关键事件。(C)2010 Wiley-Liss，Inc.
The mechanisms underlying neuropathic pain are poorly understood. However, several studies have implied a role for reactive microglia located in the dorsal horn in neuropathic pain. To clarify the roles of activated microglia in neuropathic pain, we investigated the interactions among microglia and other neural components in the dorsal horn using electron microscopy. Microglia were more abundantly localized in layers II-III of the dorsal horn than in other areas, and some of them adhered to and engulfed both injured and uninjured myelinated axons. This microglial engulfment was rarely observed in the normal dorsal horn, and the number of microglia attached to myelinated axons was markedly increased on postoperative day 7 on the operated side. However, after blocking the P2Y12 ATP receptor in microglia by intrathecal administration of its antagonist, AR-C69931MX, the increase in the number of microglia attached to myelinated axons, as well as the development of tactile allodynia, were markedly suppressed, although the number of activated microglia did not change remarkably. These results indicate that engulfment of myelinated axons by activated microglia via P2Y12 signaling in the dorsal horn may be a critical event in the pathogenesis of neuropathic pain. (C) 2010 Wiley-Liss, Inc.