Strategy for controlling intractable pain by targeting casein kinase 1 signaling system
| Project/Area Number |
25460723
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| 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 / 難治性疼痛 / カゼインキナーゼ 1 / ケミカルバイオロジー / 霊長類疼痛モデル / カゼインキナーゼ1 |
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| 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.
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.2013
Author(s)
Miura, A., Kambe, Y., Inoue, K., Tatsukawa, H., Kurihara, T., Griffin, M., Kojima, S. & Miyata, A.
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Journal Title
Journal of Biological Chemistry
Volume: 288
Issue: 45
Pages: 32720-32730
DOI
Related Report
Peer Reviewed
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[Presentation] Spinal PACAP-PAC1 signaling induces long-lasting mechanical allodynia by astroglial activation.2015
Author(s)
Miyata, A, Yokai, M., Onou, T., Kambe Y., Takasaki I., Kurihara, T
Organizer
12th international symposium on VIP/PACAP and related peptides
Place of Presentation
Cappadocia, Turkey
Year and Date
2015-09-21
Related Report
Int'l Joint Research
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[Presentation] Cross-linking of sp1 by transglutaminase 2 suppresses pac1 gene expression in neuronal cells.2013
Author(s)
Miura, A., Kambe, Y., Inoue, K., Tatsukawa, H., Kurihara, T., Kojima, S. & Miyata, A
Organizer
The 11th International Symposium on VIP, PACAP and Related Peptides
Place of Presentation
Pecs, Hungary
Related Report
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[Presentation] Acute activation of astrocytes in spinal dorsal horn via pac1 receptor is involved in PACAP-induced persistent aversive behavior2013
Author(s)
Miyata, A., Yokai, M., Ohno, T., Hasegawa, M., Kambe, Y., Inoue, K., Kamimura, Y., Shimizu, T. & Kurihara, T
Organizer
The 11th International Symposium on VIP, PACAP and Related Peptides
Place of Presentation
Pecs, Hungary
Related Report
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