Roles of T-type calcium channels and calcineurin in inflammatory or neuropathic pain
| Project/Area Number |
26460112
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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 |
Pharmacology in pharmacy
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川畑 篤史 近畿大学, 薬学部, 教授 (20177728)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | T型カルシウムチャネル / 神経障害性疼痛 / Egr-1 / USP5 / 一次知覚神経 / Cav3.2 T型カルシウムチャネル / 後根神経節 / HMGB1 / Cav3.2 T型Ca2+チャネル |
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| Outline of Final Research Achievements |
Cav3.2 T-type calcium channels (T-channels) expressed in primary sensory neurons have been known to contribute to development of various intractable pain, including somatic, visceral and neuropathic pain. In the present study, we first examined analgesic effects of RQ-00311651, a novel T-channel blocker, in various pain model animals, and have reported that the compound may serve as an orally available analgesic for treatment of neuropathic and visceral pain with minimum central side effects. We also examined the mechanism of Cav3.2 upregulation in primary sensory neurons in a neuropathic pain model induced by L5 spinal nerve cutting, which we have reported previously, and have shown that increase in expression of Egr-1, a transcription factor, and USP5, a deubiquitinating enzyme, enhances transcription of Cav3.2 and suppresses proteasomal degradation of Cav3.2, respectively, leading to upregulation and maintenance of Cav3.2 expression in primary sensory neurons after nerve injury.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Therapeutic potential of RQ-00311651, a novel T-type Ca2+ channel blocker, in distinct rodent models for neuropathic and visceral pain.2016
Author(s)
Sekiguchi F, Kawara Y, Tsubota M, Kawakami E, Ozaki T, Kawaishi Y, Tomita S, Kanaoka D, Yoshida S, Ohkubo T, Kawabata A.
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Journal Title
Pain
Volume: 157
Issue: 8
Pages: 1655-1665
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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