Role of TRPM8 in the irritable bowel syndrome like symptoms induced by early-childhood social defeat stress in mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Matsumoto Kenjiro 京都薬科大学, 薬学部, 准教授 (10406770)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 過敏性腸症候群 / 温度感受性受容体 / TRPM8 / 社会的敗北ストレス / 内臓痛覚過敏 / 知覚神経

Outline of Final Research Achievements

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder that chronically repeats abdominal pain, diarrhea and constipation. Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive, calcium-permeable cation channel identified as a receptor for menthol which provides relief from stress and mental exhaustion. The present study investigated the role of TRPM8 in IBS like symptoms induced by early-childhood social defeat stress using WT and TRPM8 deficient (KO) mice.
Juvenile social defeat stress exposure results in later onset of IBS-like symptoms in WT mice. TRPM8 expressed in sensory neuron in colon and GABAergic neuron in brain. TRPM8 deficiency attenuated the IBS like symtoms.TRPM8 has a protective role against early childhood social defeat stress induces IBS-like symptoms. TRPM8 agonist may be an attractive target for the treatment of IBS.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

世界的に高い有病率を示している過敏性腸症候群は、有用な実験動物モデルが不足している。本研究の成果は、幼少期マウス社会的敗北ストレスによる新規病態モデルを提案することができた。本病態モデルにおいてTRPM8遺伝子欠損マウスを用いた検討から、TRPM8の活性化により症状が緩和されることが示唆された。これは基礎研究からのエビデンスの乏しかった、過敏性腸症候群とTRPM8の関わりについて重要な情報となる。