Investigation of itch transmission in peripheral nerves for the development of novel molecular-targeted itch therapies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Tomoyuki Maruyama 和歌山県立医科大学, 医学部, 助教 (00894883)
• Co-Investigator(Kenkyū-buntansha): 時永 泰行 和歌山県立医科大学, 医学部, 准教授 (60438281)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: IL-31 / 痒み / Tmem45b / IL-31RA / 末梢神経 / 掻痒

Outline of Final Research Achievements

Triple staining of dorsal root ganglia of wild-type mice for IL-31RA, Tmem45b, and TRPV1 showed that a high percentage (60%) of Tmem45b-positive and TRPV1-positive cells also coexpressed IL-31-RA. When mice were intradermally treated with pruritogenic substances and the number of curettage was evaluated, Tmem45bKO mice showed significantly lower curettage with IL-31 and Compound48/80 than wild-type mice, although there was no difference in the number of curettage with solvent administration. The number of curettage was also measured in the same way in DFNB and imiqimod atopic dermatitis models. No obvious difference was observed in wild-type and KO mice.

Free Research Field

麻酔科学関連

Academic Significance and Societal Importance of the Research Achievements

本研究は、機械性痛覚過敏に関与するTmem45bがアトピー性皮膚炎の掻痒に関与していることが示され、治療薬開発の実現に有用な研究である。アトピー性皮膚炎による痒みは、掻爬行動により皮膚炎を悪化させ、更なる痒みが惹起されるという悪循環を形成し、生活の質の低下、社会的、経済的な損失に繋がる。Tmem45bは中枢神経にほとんど発現を認めず末梢の知覚神経に選択的に発現しているため、Tmem45bをターゲットとした痒み治療薬の開発は、眠気などの中枢性の副作用のない痒み治療薬の開発につながる可能性が高い。本研究は、アトピー性皮膚炎におけるかゆみ治療法を大きく発展させる核心的な治療薬開発を実現しうる。