IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain

Makoto Tsuda, Takahiro Masuda, Junko Kitano, Hiroshi Shimoyama, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue

研究成果: ジャーナルへの寄稿学術誌査読

227 被引用数 (Scopus)


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-γ (IFN-γR) 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-γR 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-γ-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-γR-dependent microglial and behavioral alterations. These results suggest that IFN-γR is a key element in the molecular machinery through which resting spinal microglia transform into an activated state that drives neuropathic pain.

ジャーナルProceedings of the National Academy of Sciences of the United States of America
出版ステータス出版済み - 5月 12 2009

!!!All Science Journal Classification (ASJC) codes

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