Cell Reports：日研究发现导致神经病变性疼痛物质

近日，日本九州大学副教授津田诚率领的研究小组发现，导致神经病变性疼痛的是一种编号为IRF8的蛋白质。相关研究报告发表在最新一期《细胞—报告》（Cell Reports）上。

神经病变性疼痛是由于癌症和糖尿病等原因损伤神经而导致的慢性疼痛，患者非常痛苦，甚至穿衣服时轻碰身体，都会非常疼痛。

此前的研究表明，神经损伤后脑和脊髓中的小神经胶质细胞过度活跃，会产生使神经兴奋的物质，从而引起疼痛。但是小神经胶质细胞为何会活跃的机制却一直没弄清。

津田诚等人在利用小鼠进行的实验中发现，IRF8蛋白质只存在于在小神胶质经细胞中。神经损伤后，小神经胶质细胞内这种蛋白质就会增加，处于活跃状态，发挥了激活小神经胶质细胞的“开关”作用。

全球约有2000万神经病变性疼痛患者，常用吗啡等麻醉药镇痛，但其效果有限而且会致人上瘾。津田诚指出：“通过遏制IRF8蛋白质的功能，就有可能缓和慢性疼痛。”研究小组今后准备继续进行研究，争取发掘现有药物遏制IRF8蛋白质的功能。（生物谷Bioon.com）

doi:10.1016/j.celrep.2012.02.014
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IRF8 Is a Critical Transcription Factor for Transforming Microglia into a Reactive Phenotype

Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Hidetoshi Tozaki-Saitoh, Keiko Ozato, Tomohiko Tamura, Kazuhide Inoue

Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-overexpressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation.