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The Research for the Mechanism of Chronically Intractable Pain Based on the Functions of Microglia as Brain Immunocompetent Cell

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Chronic Inflammation

Abstract

Injury to the nervous system often causes a debilitating chronic pain syndrome, termed neuropathic pain. Neuropathic pain is refractory to currently available analgesics. Accumulating evidence indicates that spinal microglia react and undergo a series of changes that influence directly establishing the pain. P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in spinal microglia after nerve injury by several factors including the CC chemokine CCL21 derived from damaged neurons, CC chemokine receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord, and the transcription factor interferon regulatory factor 8 and 5 expressed in microglia. The inhibition of the function of P2X4R and P2X4R-regulating molecules suppresses the excitability of dorsal horn neurons and neuropathic pain. These findings indicate that microglia overexpressing P2X4R are a central player in neuropathic pain.

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Author information

Authors and Affiliations

  1. Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kazuhide Inoue

  2. AMED-CREST, Fukuoka, 812-8582, Japan

    Kazuhide Inoue

  3. Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Makoto Tsuda

Authors
  1. Kazuhide Inoue
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  2. Makoto Tsuda
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Correspondence to Kazuhide Inoue .

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Editors and Affiliations

  1. Interdisciplinary Program for Biomedical Sciences Institute for Academic Initiatives, Osaka University, Suita, Japan

    Masayuki Miyasaka

  2. Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Kiyoshi Takatsu

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Inoue, K., Tsuda, M. (2016). The Research for the Mechanism of Chronically Intractable Pain Based on the Functions of Microglia as Brain Immunocompetent Cell. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_48

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