| Project/Area Number |
17K09042
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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 |
Pain science
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 扁桃体 / 腕傍核 / シナプス可塑性 / モノアミン / 神経生理 / 神経科学 |
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| Outline of Final Research Achievements |
Chronic pain is characterized by plastic changes in the brain networks. This study was undertaken to reveal the mechanism of pain chronification focusing on noradrenaline as an enhancer of plastic changes in pain network. We used a transgenic rat line, DBH-tTA-2A-Cre BAC Tg rat, to induce intrinsic noradrenaline release and analyze the effect of noradrenaline release on a pivotal synapse in pain pathway, the synapse between lateral parabrachial nucleus and central nucleus of the amygdala capsular part (LPB-CeC synapse). We injected AAV vector into a noradrenergic nucleus, nucleus solitary of tract, to express channelrhodopsin with cre-dependent manner. In acute brain slices, we induced intrinsic noradrenaline release by blue light and recorded light-evoked EPSCs in LPB-CeC synapse. We could observe slight synaptic modulation of noradrenaline and the effect of noradrenaline was enhanced by duloxietine, suggesting that the intrinsic noradrenaline release might be volume transmission.
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| Academic Significance and Societal Importance of the Research Achievements |
ノルアドレナリン神経特異的Creリコンビナーゼ発現ラットと光遺伝学技術を組み合わせ、内因性ノルアドレナリン放出を誘発し、ノルアドレナリンのvolume transmissionを示唆するシナプス伝達修飾作用を捉えることに成功した。また、ペインマトリクス全体の痛みの慢性化過程での脳活動の可視化、および、それに対する経路特異的活動介入評価が可能な小動物MRIの実験系を得ることができ、痛みの慢性化におけるノルアドレナリン神経やその他の特異的な経路の役割解明の技術基盤を得た。これらの実験事実、実験手法に基づき今後研究を発展させることで、慢性痛治療における新たな治療標的の提示が期待される。
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