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标题：IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain
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作者：Makoto Tsuda ; Takahiro Masuda ; Junko Kitano 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：19
页码：8032-8037
DOI：10.1073/pnas.0810420106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Neuropathic pain, a highly debilitating pain condition that commonly occurs after nerve damage, is a reflection of the aberrant excitability of dorsal horn neurons. This pathologically altered neurotransmission requires a communication with spinal microglia activated by nerve injury. However, how normal resting microglia become activated remains unknown. Here we show that in naive animals spinal microglia express a receptor for the cytokine IFN-{gamma} (IFN-{gamma}R) in a cell-type-specific manner and that stimulating this receptor converts microglia into activated cells and produces a long-lasting pain hypersensitivity evoked by innocuous stimuli (tactile allodynia, a hallmark symptom of neuropathic pain). Conversely, ablating IFN-{gamma}R severely impairs nerve injury-evoked microglia activation and tactile allodynia without affecting microglia in the contralateral dorsal horn or basal pain sensitivity. We also find that IFN-{gamma}-stimulated spinal microglia show up-regulation of Lyn tyrosine kinase and purinergic P2X4 receptor, crucial events for neuropathic pain, and genetic approaches provide evidence linking these events to IFN-{gamma}R-dependent microglial and behavioral alterations. These results suggest that IFN-{gamma}R is a key element in the molecular machinery through which resting spinal microglia transform into an activated state that drives neuropathic pain.
关键词：allodynia ; cytokine ; glia ; Lyn tyrosine kinase ; purinergic receptor