2016 Fiscal Year Final Research Report
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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| Project Period (FY) |
2014-04-01 – 2017-03-31
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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 |
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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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| Free Research Field |
薬理学
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