Modulation of descending pain system due to social stress

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K23120
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Nihon University
• Principal Investigator: KAWASAKI Shiori 日本大学, 歯学部, 専修研究員 (30876397)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 中脳水道周囲灰白質 / コリン作動性ニューロン / ムスカリン受容体 / GIRKチャネル

Outline of Final Research Achievements

In this study, we focused on the periaqueductal gray (PAG) which is a pivotal area to regulate pain. Cholinergic neurons at PAG showed high-frequency spontaneous firing. Application of a muscarinic agonist to cholinergic neurons in PAG induced rapid hyperpolarization by opening G protein-activated inwardly rectifying potassium (GIRK) channels went through muscarinic 2(M2) receptors. Additionally, neostigmine, an inhibitor of choline esterase, which indirectly increases acetylcholine in the synaptic cleft, also evoked rapid hyperpolarization. These results suggested that cholinergic neurons in PAG regulate neural excitability via M2 receptors, which link to GIRK channels and autocrine or paracrine of acetylcholine are likely involved in this cholinergic regulation of neural firing.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

中脳水道周囲灰白質のコリン作動性ニューロンに発現するムスカリン2（M2）受容体がアセチルコリンの自己分泌もしくは傍分泌によって活性化し、受容体に共役するGタンパク質活性型内向き整流性（GIRK）カリウムチャネルが開口して過分極することで自己興奮を制御している可能性について示した。中脳水道周囲灰白質は疼痛制御の要衝であり、本研究で得られた成果は既存の疼痛治療に対して抵抗性のものに対して新たな創薬ターゲットとして期待される。