Identification of the role of noradrenaline system in the enhanced nociception-emotion link in chronic pain

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09042
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Jikei University School of Medicine
• Principal Investigator: TAKAHASHI YUKARI 東京慈恵会医科大学, 医学部, 助教 (20613764)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 扁桃体 / 腕傍核 / シナプス可塑性 / モノアミン / 神経生理

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.

Free Research Field

神経科学

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。