| Project/Area Number |
17H04113
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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 |
Pain science
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
Noguchi Koichi 兵庫医科大学, 医学部, 学長・教授 (10212127)
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| Co-Investigator(Kenkyū-buntansha) |
山中 博樹 兵庫医科大学, 医学部, 講師 (20340995)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | 神経障害性疼痛 / プロテアーゼ / 脊髄後角 / シナプス可塑性 / 細胞間接着 |
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| Outline of Final Research Achievements |
In this study, we investigated the synchronized alterations in α2δ-1, L1-CAM and phoshorylated L1-CAM expression patterns in the injured c-fibers following peripheral nerve injury. These molecules were co-localized in hypertrophic varicosities in the central terminals of injured c-fibers of neuropathic pain model rats. Quantitative analyses revealed that the peripheral nerve injury reduced dendritic synaptic contacts but promoted aberrant axo-axonic contacts on the hypertrophic varicosities in which α2δ-1, L1-CAM and pL1-CAM were present. In the dorsal horn, administration of the anti-allodynic drug pregabalin inhibited the increase in α2δ-1 expression and suppressed the hypertrophy of L1-CAM labeled varicosities. Our findings highlight the formation of aberrant spinal circuits that mediate the convergence of local neuronal signals onto injured c-fibers, suggesting that these hypertrophic varicosities may be important in the mechanisms underlying neuropathic pain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題の成果は難治性疼痛である神経傷害性疼痛のメカニズムとして可視化できるシナプス結合様式の変化を想定できた事に学術的な意義をもつ。また形態変化の現場に発現する再生・形態変化関連の分子を治療戦略ターゲットをとして研究対象とする事で、対象とする分子群を想定できる。また、in vitroの実験系でも形態変化のアッセイが可能となることから、in viroからの還元できる実験系を豊富に想定できる事になる。本研究が目指した形態変化と疼痛の関連を明らかにできれば新たな治療・創薬などの可能性を広げる社会的意義を持つと思われる。
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