Mechanisms for increase of TRP channels in visceral hypersensitivity in inflammatory and functional bowel disease model animals

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06688
• 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: Josai International University
• Principal Investigator: HORIE SYUNJI 城西国際大学, 薬学部, 教授 (50209285)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 温度感受性TRPチャネル / 内臓痛覚過敏 / 求心性一次知覚神経 / 過敏性腸症候群 / TRPM8 / TRPV1 / CGRP / 微細炎症

Outline of Final Research Achievements

In irritable bowel syndrome (IBS) model rats, we investigated the involvement of TRPM8 in visceral hyperalgesia.
In the rectal histology of IBS model rats, the number of TRPM8-expressing nerve fibers in the mucosal layer and cell bodies in the myenteric plexus significantly increased compared with normal rats. In behavioral observation, the number of cooling substance-induced visceral pain-like behaviors increased. These results suggest that the increase of TRPM8-expressing neurons is involved in visceral hyperalgesia in IBS model animal.
The reduction of the neurons is a novel therapeutic strategy for teatment of visceral hyperalgesia in IBS.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

当該研究では過敏性腸症候群モデル動物における温度感受性TRPM8の発現神経数の増加や活性増大のメカニズムについて検討した。世界的な消化器病診断新基準Rome IVが定まり、過敏性腸症候群の患者数が急増し、消化管知覚過敏性に対する治療法の確立は社会的に急務となってきている。当該研究の成果は、この消化管知覚過敏性の原因に対してひとつの仮説を提案した。また、粘膜炎症を抑えることでTRPチャネル発現神経線維数の増加が抑制され、知覚過敏性を抑えられるという新しい治療法の開発へ応用できる。