Development of curative treatment against neuropathic pain through comprehensive functional analysis of human long non-coding RNAs
| Project/Area Number |
16H05461
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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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) |
齋藤 文仁 日本医科大学, 医学部, 准教授 (20360175)
坂本 篤裕 日本医科大学, 大学院医学研究科, 大学院教授 (30196084)
坂井 敦 日本医科大学, 医学部, 講師 (30386156)
丸山 基世 日本医科大学, 医学部, 助教 (60709757)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | H19 / Neat1 / 一次感覚神経 / 後根神経節 / 神経障害性疼痛 / 脊髄神経結紮 / 長鎖ノンコーディングRNA / ヒトiPS細胞 / 神経科学 / 核酸 / 脳神経疾患 / マイクロアレイ / 薬理学 / RNA シーケンス |
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| Outline of Final Research Achievements |
Neuropathic pain is intractable chronic pain mainly caused by damage of the primary sensory nerve. Because clinical benefits of available analgesics are insufficient for the patients with neuropathic pain, the possible novel therapeutic strategy based on the pathophysiology of long non-coding RNAs (lncRNAs), key regulators of gene expression, was investigated. Expression changes in several lncRNAs were shown in the primary sensory neurons after nerve injury in rats. Among them, the lncRNA Neat1 was significantly upregulated in the DRG after the nerve injury. Down-regulation of Neat1 alleviated mechanical allodynia and thermal hyperalgesia. Analysis using human primary sensory neurons differentiated from iPS cells revealed that lncRNAs expression was changed after the injury-mimicking stimuli as observed in the animal model of neuropathic pain.
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| Academic Significance and Societal Importance of the Research Achievements |
神経障害性疼痛は慢性化し難治化する疼痛疾患であり、有効な治療薬がない。神経障害性疼痛の中で最も発症頻度の高い一次感覚神経（末梢神経）障害に焦点を当て、新たな着想に基づいた治療薬を開発することは、医療上重要な課題である。一方、生物種差が大きいヒトlncRNAは、疼痛病態における機能は未解明である。モデル動物とヒト細胞を駆使し、神経障害性疼痛で変動するlncRNAを同定し機能を明らかにしたことは、新規治療標的の可能性を示すものであり、新しい末梢神経障害の根治治療に繋がる点で社会的意義が大きい。
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Report
(5 results)
Research Products
(41 results)
