| Project/Area Number |
16K10816
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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 |
Orthopaedic surgery
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| Research Institution | University of Toyama |
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Principal Investigator |
SEKI Shoji 富山大学, 大学院医学薬学研究部(医学), 助教 (00432112)
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| Co-Investigator(Kenkyū-buntansha) |
川口 善治 富山大学, 大学院医学薬学研究部(医学), 准教授 (00262527)
箭原 康人 富山大学, 附属病院, 医員 (60456390)
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| Research Collaborator |
NOGAMI makiko
MAKINO hiroto
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | AP-1阻害剤 / 腰椎椎間板 / 椎間板穿刺モデル / 腰痛症 / 脊椎脊髄病学 |
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| Outline of Final Research Achievements |
Lumbar intervertebral disc (IVD) degeneration is attributable mainly to LBP, called discogenic pain, which often leads to disc herniation presenting as sciatica. We investigated the effects of inhibition of c-Fos/AP-1（T-5224）on IVD degeneration and associated pain. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of x-ray, MRI findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. T-5224 prevented disc degeneration, and oral administration of T-5224 extended the tail flick latency as a measure of heat stimulation in the rat tail-puncture model. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain.
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| Academic Significance and Societal Importance of the Research Achievements |
腰椎椎間板変性は、脊柱管狭窄症、ヘルニア、腰痛の原因の一つである。これらの疾患は若年-中高年まで労働生産性の高い年代に患うことが多い。現在臨床応用可能な椎間板変性抑制の薬はなく、早期臨床応用可能な治療法の開発は急務である。椎間変性が抑制できれば、多くの腰痛や狭窄症に悩む患者にとって非常に朗報である。c-fos/AP-1阻害薬（T-5224）は、動物実験レベルでは椎間板変性抑制作用とその関連痛を抑制した。この薬は実際にヒトへの投与も可能であり、実際に臨床的効果が得られれば、労働生産性の向上など社会的利益も大きい点で、極めて有益な研究であると確信する。
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