| Project/Area Number |
16K15340
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pain science
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SUZUKI HIDENORI 日本医科大学, 大学院医学研究科, 大学院教授 (30221328)
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| Co-Investigator(Kenkyū-buntansha) |
坂井 敦 日本医科大学, 医学部, 講師 (30386156)
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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 |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 変形性膝関節症 / 核酸医薬 / マイクロRNA / 神経障害性疼痛 / 一次感覚神経 / エクソソーム / マイクロRNAクラスター / 滑膜 / 前十字靭帯断裂 / 核酸 / 神経科学 / 生体分子 / 脳神経疾患 / 薬理学 |
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| Outline of Final Research Achievements |
Exosomes are extracellular vesicles containing RNAs and proteins, and play a role in cell-to-cell communication. Therefore, they can work as a target-specific drug delivery system for RNA medicine. MicroRNA (miRNA) post-transcriptionally regulates the expression of many specific genes. In this study, we searched for potential miRNAs present in exosomes as candidates to develop novel drugs for the treatment of neuropathic pain. In knee osteoarthritis (OA) model rats with neuropathic pain, we found that the miRNA miR-21 was released from the synovial tissue and increased in the synovial fluid in OA model rats. A single intra-articular injection of miR-21 inhibitor (modified RNAs) exerted long-term analgesia in OA rats, while miR-21 injection caused knee joint pain through Toll-like receptor 7, which was expressed in the primary afferent neurons in naive rats. These results suggest that miR-21-blocking nucleic acids have a clinical potential against OA with neuropathic pain.
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| Academic Significance and Societal Importance of the Research Achievements |
がん、糖尿病あるいは外傷など様々な疾患に起因する難治性神経障害性疼痛に対する疼痛管理は、現在の医療において患者のQOL を改善するために重要な課題の1 つである。現在使用されている抗てんかん薬、抗うつ薬やオピオイド等の鎮痛薬は効果が限定的であり、有害反応も少なくない。さらに、これらの治療薬は本疾患の病態に基づく合理的かつ特異的な治療手段となり得ていない。本研究の成果は、病態生理に基づき、miRNA関連分子による新たな神経障害性疼痛に対する治療薬の開発基盤を提供する点で、学術的・社会的意義が大きいと考えられる。
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