ID | 53954 |
フルテキストURL | |
著者 |
Nakamura, Yoki
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
Morioka, Norimitsu
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
Abe, Hiromi
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
Zhang, Fang Fang
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
Hisaoka-Nakashima, Kazue
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
Liu, Keyue
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmacological Sciences, Okayama University
Nishibori, Masahiro
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmacological Sciences, Okayama University
Kaken ID
publons
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Nakata, Yoshihiro
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
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抄録 | High mobility group box-1 (HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that intravenous injection of anti-HMGB1 monoclonal antibody significantly attenuated brain edema in a rat model of stroke, possibly by attenuating glial activation. Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating peripheral nerve injury-induced pain. Following partial sciatic nerve ligation (PSNL), rats were treated with either anti-HMGB1 or control IgG. Intravenous treatment with anti-HMGB1 monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile hypersensitivity at 7, 14 and 21 days, but not 3 days, after ligation, whereas control IgG had no effect on tactile hypersensitivity. The expression of HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of HMGB1 protein. Also, the injury-induced translocation of HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of HMGB1. Markers of astrocyte (glial fibrillary acidic protein (GFAP)), microglia (ionized calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the sham-operated side 21 days after PSNL. Anti-HMGB1 monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of neuropathic pain. Thus, the targeting of HMGB1 could be a useful therapeutic strategy in the treatment of chronic pain.
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備考 | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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発行日 | 2013-08-21
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出版物タイトル |
PLOS ONE
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巻 | 8巻
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号 | 8号
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出版者 | PUBLIC LIBRARY SCIENCE
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開始ページ | e73640
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ISSN | 1932-6203
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1371/journal.pone.0073640
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言語 |
英語
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著作権者 | © 2013 Nakamura et al.
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論文のバージョン | publisher
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査読 |
有り
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DOI | |
PubMed ID | |
Web of Science KeyUT |