MISC

2016年2月

Perineural expression of high-mobility group box-1 contributes to long-lasting mechanical hypersensitivity via matrix metalloprotease-9 up-regulation in mice with painful peripheral neuropathy

JOURNAL OF NEUROCHEMISTRY
  • Fang Fang Zhang
  • ,
  • Norimitsu Morioka
  • ,
  • Sakura Harano
  • ,
  • Yoki Nakamura
  • ,
  • Keyue Liu
  • ,
  • Masahiro Nishibori
  • ,
  • Kazue Hisaoka-Nakashima
  • ,
  • Yoshihiro Nakata

136
4
開始ページ
837
終了ページ
850
記述言語
英語
掲載種別
DOI
10.1111/jnc.13434
出版者・発行元
WILEY-BLACKWELL

High-mobility group box-1 (HMGB1) has been shown to be critical in the modulation of nociceptive transduction following a peripheral neuropathy. However, the precise role of peripherally expressed HMGB1 in neuropathic pain has yet to be fully elaborated. Following a partial sciatic nerve ligation (PSNL) in mice, a persistent ipsilateral up-regulation of HMGB1 was observed from 3 to 21days after PSNL, in paralleled with a robust ipsilateral hind paw mechanical hypersensitivity. Increased HMGB1 was detected in both infiltrating macrophages and proliferating Schwann cells in the ipsilateral nerve 14days following PSNL. Repeated perineural treatment with anti-HMGB1 antibody significantly ameliorated PSNL-induced mechanical hypersensitivity. Several pronociceptive molecules, including matrix metalloprotease-9 (MMP-9), tumor necrosis factor-, interleukin-1 (IL-1), and cyclooxygenase-2, were up-regulated in injured sciatic nerve 14days following PSNL. Repeated perineural treatment with an anti-HMGB1 antibody significantly suppressed expression of MMP-9, but not other pronociceptive molecules. Perineural treatment with a selective MMP-9 inhibitor ameliorated PSNL-induced mechanical hypersensitivity. The current findings demonstrate that the maintenance of the neuropathic state following an injured nerve is dependent on the up-regulation of HMGB1 and MMP-9. Thus, blocking HMGB1 function in sciatic nerve could be a potent therapeutic strategy for the treatment of neuropathic pain.

Web of Science ® 被引用回数 : 18

リンク情報
DOI
https://doi.org/10.1111/jnc.13434
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000369145200016&DestApp=WOS_CPL

エクスポート
BibTeX RIS