MISC

2016年7月

Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

TOXICOLOGY
  • Takeshi Nishida
  • ,
  • Maho Tsubota
  • ,
  • Yudai Kawaishi
  • ,
  • Hiroki Yamanishi
  • ,
  • Natsuki Kamitani
  • ,
  • Fumiko Sekiguchi
  • ,
  • Hiroyasu Ishikura
  • ,
  • Keyue Liu
  • ,
  • Masahiro Nishibori
  • ,
  • Atsufumi Kawabata

365
開始ページ
48
終了ページ
58
記述言語
英語
掲載種別
DOI
10.1016/j.tox.2016.07.016
出版者・発行元
ELSEVIER IRELAND LTD

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Web of Science ® 被引用回数 : 19

リンク情報
DOI
https://doi.org/10.1016/j.tox.2016.07.016
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000382415400006&DestApp=WOS_CPL

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