Role of thermo-sensitive TRPV1 and TRPM8 channels in visceral hypersensitivity in inflammatory bowel disease model animals and ulcerative colitis patients

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Josai International University
• Principal Investigator: Horie Syunji 城西国際大学, 薬学部, 教授 (50209285)
• Research Collaborator: HOSOYA Takuji ; YAMAKAWA Takumi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 潰瘍性大腸炎 / 温度感受性TRPチャネル / 知覚過敏 / 痛覚過敏 / 知覚神経 / 過敏性腸症候群 / TRPV1 / TRPM8

Outline of Final Research Achievements

We investigated the involvement of TRPM8 in hyperalgesia in normal and experimental colitis and irritable bowel syndrome (IBS) model animals.
TRPM8 immunoreactivity in the distal colon was much higher than in the transverse and proximal colon under physiological conditions. TRPM8 immunoreactivity markedly increased in the distal colon mucosa of colitis model mice compared with the control mice. The number of TRPM8 nerve fibers in mucosa of colitis model mice drastically increased compared with the control. Intracolonic administration of WS-12 induced behavioral visceral pain-like responses. The numbers of these responses in the colitis model were 3 times higher than in the control, and were decreased by pretreatment with the TRPM8 channel blocker AMTB. In IBS model, the number of TRPM8 nerve fibers in mucosa of butyrate-induced IBS model also increased compared with the control. Increased expression of TRPM8 may contribute to the visceral hyperalgesia of experimental colitis and IBS.

Free Research Field

神経消化器病の原因究明と医薬品の薬効評価