2021 Fiscal Year Final Research Report

Discovery of novel target molecules that regulate discogenic pain by investigating of the mechanism of suppressive action by prostaglandins.

Research Project

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Project/Area Number	17K11028
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Orthopaedic surgery
Research Institution	Tokyo Medical University
Principal Investigator	Suzuki Hidekazu 東京医科大学, 医学部, 兼任講師 (40317871)
Co-Investigator(Kenkyū-buntansha)	山本謙吾東京医科大学, 医学部, 主任教授 (10246316) 澤地恭昇東京医科大学, 医学部, 講師 (20571152) 遠藤健司東京医科大学, 医学部, 准教授 (90266479) 松岡佑嗣東京医科大学, 医学部, 兼任助教 (50408126) 高松太一郎東京医科大学, 医学部, 助教 (90459561) 関健東京医科大学, 医学部, 助教 (40617669)
Project Period (FY)	2017-04-01 – 2022-03-31
Keywords	椎間板性疼痛 / 神経侵入 / DUSP-1 / NGF
Outline of Final Research Achievements	Discogenic pain is caused by the invasion of nerve fibers responsible for pain sensation into the inner part of degenerated intervertebral disc. Nerve growth factor (NGF) plays an important role in this process, however, a mechanism of the regulation of NGF expression has been unknown. We have previously shown that NGF expression in human intervertebral disc cells increases when PGE2 production is suppressed by selective COX-2 inhibitors commonly used to treat low back pain, and conversely its expression is suppressed by treating the cells with exogenous PGE2 or PGE1. In this study, PGE1/2 was found to suppressively regulate NGF induction by attenuating MAP kinase pathway, an intracellular signaling pathway, and this was confirmed to be due to the induction of DUSP-1. The study will shed light on new insight for the development of therapeutic approach to treat low back pain by targeting DUSP-1.
Free Research Field	整形外科学
Academic Significance and Societal Importance of the Research Achievements	ヒト椎間板細胞において，PGE1/2はDUSP-1発現を誘導することにより炎症刺激で活性化されるMAP kinaseのリン酸化を抑制し，NGF発現を抑制的に調節するといった新たな生理・薬理作用を有することが初めて明らかとなった．椎間板性疼痛の保存治療は，依然としてPGE2産生抑制を目的とした選択的COX-2阻害剤等による対症療法が主でありその効果は限定的である．本研究により見出したDUSP-1によるNGF発現抑制作用は，椎間板性疼痛の病態を直接的に制御しうる新たな原因療法に繋がることが期待され，学術的，社会的意義の高い研究成果と言える．