Strategy for controlling intractable pain by targeting casein kinase 1 signaling system

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kagoshima University
• Principal Investigator: Kurihara Takashi 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
• Co-Investigator(Renkei-kenkyūsha): Hagiwara Masatoshi 京都大学, 大学院医学研究科, 教授 (10208423) ; Yoshimura Megumu 熊本保健科学大学, 大学院保健学研究科, 教授 (10140641)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経障害性疼痛 / 炎症性疼痛 / 脊髄 / リン酸化酵素 / vacuolar-ATPase / Wntシグナル

Outline of Final Research Achievements

In this study, we have focused on the spinal and sensory CK1 signaling system as potential useful targets for analgesic drug development, and evaluated the vacuolar ATPase (vATPase) and Wnt3a signaling pathway as possible candidates. Consequently, we found that intrathecal administration of a vATPase inhibitor, bafilomycin A1, and Wnt3a, significantly alleviated the expression of spinal nerve injury-induced mechanical allodynia, and produced mechanical allodynia, respectively. We have also constructed new screening system for the identification of novel CK1 inhibitors. Some of newly identified CK1 inhibitors showed antinociceptive effects on acute and persistent inflammatory pain models in mice. Our data indicate that evaluating spinal and sensory CK1 signaling system would be promising to identify potential useful targets for analgesic drug development.

Free Research Field

医歯薬学