Exploring for pain-related molecules that induce mechanical hyperalgesia for the development of new pain therapeutics

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16460
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Tadashi Tanioku 和歌山県立医科大学, 医学部, 助教 (50554656)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 機械性痛覚過敏

Outline of Final Research Achievements

The present study was designed to search for unknown pain-related molecules that are important for the generation of mechanical hyperalgesia. In this study, we analyzed Tmem45b, which is expressed on the IB4 binding neuron, and found that the IB4 junctional nerve selectively transmits mechanical hyperalgesia induced by inflammation. In this study, we analyzed the expression and function of Tmem45b, which is expressed on IB4 binding neurons.
In this study, we analyzed the expression and function of Tmem45b, which is expressed on the IB4 binding neuron, and confirmed that Tmem45b is a small peripheral nerve-specific molecule with little expression in the central nervous system. Functional analysis using Tmem45b knockout mice revealed that Tmem45b is not involved in pain transmission in physiological conditions, but is selectively involved in the development of mechanical hyperalgesia induced by inflammation.

Free Research Field

痛み

Academic Significance and Societal Importance of the Research Achievements

手術後、外傷後、がんなどの炎症性病態では機械刺激による痛みが増幅される機械性痛覚過敏が生じ患者を苦痛に陥れる。機械性痛覚過敏が発生する分子メカニズムは不明で有り新たな鎮痛薬の開発は進んでいない。
本研究では、炎症によって惹起される機械性痛覚過敏の責任分子としてTmem45bを同定した。また、Tmem45bは中枢神経にほとんど発現せず末梢神経特異的に発現するという特徴を有することを確認した。現在鎮痛薬として用いられているオピオイドは中枢神経に作用することに起因する副作用が問題となっている。もしTmem45bをターゲットした新薬が開発されるならば中枢性副作用を有しない画期的な鎮痛薬となり得る。