2019 Fiscal Year Final Research Report

Basic research on a treatment for pain targeting primary afferent A nerve fibers

Research Project

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Project/Area Number	17K09043
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Pain science
Research Institution	Nihon University
Principal Investigator	TSUBOI Yoshiyuki 日本大学, 歯学部, 講師 (50246906)
Co-Investigator(Kenkyū-buntansha)	浅野正岳日本大学, 歯学部, 教授 (10231896) 奥村雅代松本歯科大学, 歯学部, 講師 (10362849) 三枝禎日本大学, 松戸歯学部, 教授 (50277456)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	A神経線維 / QX-314 / フラジェリン
Outline of Final Research Achievements	QX-314 (Q) is a derivative of lidocaine and block the conduction by binding Na+ channel. Flagellin (F) is a ligand of the Toll-like receptor 5. Recently, it has been reported that Q/F solution selectively blocked Aβ fibers in mice. The purpose of this study clarifies the effects of Q/F on the conduction of the sciatic nerve and thresholds for mechanical stimulation to foot in rats. Compound action potentials were recorded from the dorsal roots of lumber 4 or 5 following the electrical stimulation of sciatic nerve (SN) at the level of the distal of the mid-thigh under gas anesthesia. Aβ fibers were first blocked by the application of Q/F solution in dose and infusion-velocity dependent manner. But the solution also finally blocked other types of fiber. Thresholds for mechanical stimulation to foot were increased in rats with SN injury at 40 min to 3 h after Q/F solution injection to foot skin. These results suggest that Q/F solution may be required any contrivance for the application.
Free Research Field	神経科学
Academic Significance and Societal Importance of the Research Achievements	神経、特に末梢神経が障害されたときに疼痛が発症する（神経障害性疼痛）。その疼痛は、正常時には無害な（低閾値）機械刺激により激烈な痛みが生じるアロディニアを主症状とする。低閾値機械刺激情報はAβ神経により伝導される。QX-314(Q)はリドカインの誘導体であり、Na+チャネルに結合して神経伝導をブロックする。Flagellin(F)は、Toll-like受容体5のリガンドである。Q/F溶液投与は、最初にAβ神経を容量依存性にブロックすること、神経障害モデル動物の閾値の上昇（痛くなる刺激の強さが大きくなる）が示唆され、その投与法の工夫をすればアロディニアに対する治療となることが期待できる。