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

Molecular Pain

Atsuro Miyata³  Masatoshi Hagiwara¹  Megumu Yoshimura⁴  Tsutomu Tanabe²  Toshihide Asada³  Daisuke Kawamoto³  Isao Kii¹  Masayasu Toyomoto¹  Eri Sakurai²  Takashi Kurihara² 

[1] Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima 890-8544, Japan;Graduate School of Health Sciences, Kumamoto Health Science University, 325 Izumi-machi, Kumamoto 861-5598, Japan

关键词: Whole-cell patch-clamp;    Hyperalgesia;    CFA;    Complete Freund’s adjuvant;    Carrageenan;    Allodynia;   

Others  :  861773
DOI  :  10.1186/1744-8069-10-17

 received in 2013-12-02, accepted in 2014-03-02,  发布年份 2014

【 摘 要 】

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 μM) or IC261 (1 μM) 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.

【 授权许可】

   
2014 Kurihara et al.; licensee BioMed Central Ltd.

【 图 表 】

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