Identification of interaction mechanisms of two descendign pathways using circuit specific gene manupulation methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15206
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Keisuke Koga 兵庫医科大学, 医学部, 助教 (50835189)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 痛み / 脊髄 / 青斑核 / ノルアドレナリン / 吻側延髄腹内側部

Outline of Final Research Achievements

Pain is an alert system in our body which notify potential or actual thread to us, but excessive pain significantly deteriorates our quality of life, and effective cares and treatments need to be developed. In this study, to identify new circuit mechanisms controlling pain, we focused on descending systems, especially on the rostral ventromedial medulla (RVM), the locus coeruleus (LC). We found that several LC neurons project to the RVM, and activation of this LC→RVM circuit decreased thermal pain sensitivity. We further investigated underlying molecular mechanisms of this behavior and performed patch-clamp recording from retrogradely labeled spinal cord (SC) projecting RVM neurons. (RVM→sc neurons). RVM→sc neurons exhibited depolarization and subsequent action potential firings by application of noradrenaline, and these responses were mediated a specific adrenergic receptor. These findings were crucial for development of new drugs for pain by using internal descending pathways

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

脳幹背側部に位置するノルアドレナリン（NA）神経核のLCは、脊髄を含む様々な脳領域に投射し、覚醒や注意・意識・認知などの生理機能と疼痛の制御に関与する。近年、疼痛制御におけるLC神経の脊髄や前頭前皮質への神経投射特異的な役割が報告された。しかし、LC神経は下行性神経核である吻側延髄腹内側部（RVM）にも投射するがその疼痛制御における役割は解明されておらず、2つの下行性神経核の相互作用機序は依然として不明である。本研究は回路特異的な神経活動操作法によりLC→RVM神経回路の疼痛制御における役割を明らかにする研究であり、下行性疼痛制御回路を利用した新規の鎮痛薬の開発に繋がることが期待される。