論文

査読有り
2014年3月

Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors

MOLECULAR PAIN
  • Takashi Kurihara
  • ,
  • Eri Sakurai
  • ,
  • Masayasu Toyomoto
  • ,
  • Isao Kii
  • ,
  • Daisuke Kawamoto
  • ,
  • Toshihide Asada
  • ,
  • Tsutomu Tanabe
  • ,
  • Megumu Yoshimura
  • ,
  • Masatoshi Hagiwara
  • ,
  • Atsuro Miyata

10
開始ページ
17
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/1744-8069-10-17
出版者・発行元
BIOMED CENTRAL LTD

Background: The phylogenetically highly conserved CK1 protein kinases consisting of at least seven isoforms form a distinct family within the eukaryotic protein kinases. CK1 family members play crucial roles in a wide range of signaling activities. However, the functional role of CK1 in somatosensory pain signaling has not yet been fully understood. The aim of this study was to clarify the role of CK1 in the regulation of inflammatory pain in mouse carrageenan and complete Freund's adjuvant (CFA) models.
Results: We have used two structurally different CK1 inhibitors, TG003 and IC261. TG003, which was originally identified as a cdc2-like kinase inhibitor, had potent inhibitory effects on CK1 isoforms in vitro and in cultured cells. Intrathecal injection of either TG003 (1-100 pmol) or IC261 (0.1-1 nmol) dose-dependently decreased mechanical allodynia and thermal hyperalgesia induced by carrageenan or CFA. Bath-application of either TG003 (1 mu M) or IC261 (1 mu M) had only marginal effects on spontaneous excitatory postsynaptic currents (sEPSCs) recorded in the substantia gelatinosa neurons of control mice. However, both compounds decreased the frequency of sEPSCs in both inflammatory pain models.
Conclusions: These results suggest that CK1 plays an important pathophysiological role in spinal inflammatory pain transmission, and that inhibition of the CK1 activity may provide a novel strategy for the treatment of inflammatory pain.

Web of Science ® 被引用回数 : 16

リンク情報
DOI
https://doi.org/10.1186/1744-8069-10-17
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000334887500001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1186/1744-8069-10-17
  • ISSN : 1744-8069
  • Web of Science ID : WOS:000334887500001

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