IFN-γreceptor signaling mediates spinal microglia activation driving neuropathic pain

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IFN-γreceptor signaling mediates spinal microglia activation driving neuropathic pain

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Article
Kyushu Univ. Production Kyushu Univ. Production
Responsibility:
Tsuda, Makoto(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Masuda, Takahiro(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Kitano, Junko(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)

Shimoyama, Hiroshi(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Tozaki-Saitoh, Hidetoshi(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Inoue, Kazuhide(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
津田, 誠(九州大学大学院薬学研究院臨床薬学部門)
増田, 隆博(九州大学大学院薬学研究院臨床薬学部門)
北野, 順子(九州大学大学院薬学研究院臨床薬学部門)
下山, 裕(九州大学大学院薬学研究院臨床薬学部門)
齊藤, 秀俊(九州大学大学院薬学研究院臨床薬学部門)
井上, 和秀(九州大学大学院薬学研究院臨床薬学部門)

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Language:
English
Publication info:
Proceedings of the National Academy of Sciences. 106, (19), pp. 8032-8037-, 2009-05-12. National Academy of Sciences
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Author
Abstract:
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. Read more
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