Roles of ROS-sensitive TRP channels in generation and prolongation of pain and dysesthesia

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293019
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Nakagawa Takayuki 京都大学, 医学(系)研究科(研究院), 准教授 (30303845)
• Co-Investigator(Renkei-kenkyūsha): SHIRAKAWA Hisashi 京都大学, 大学院薬学研究科, 准教授 (50402798) ; MORI Yasuo 京都大学, 大学院工学研究科, 教授 (80212265)
• Research Collaborator: SO Kanako ; DOGISHI Koji ; ISAMI Koichi ; MIYAKE Takahito ; KODERA Mizuki ; OYAMA Shohei ; SUKEISHI Asami ; TEI Yuna ; HIYAMA Haruka
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: TRPチャネル / 活性酸素種 / 痛み / しびれ / オキサリプラチン / TRPA1 / TRPM2 / 慢性膀胱炎

Outline of Final Research Achievements

It is well known that reactive oxygen species (ROS) nonspecifically impairs sensory neurons, which generate unpleasant abnormal sensation, such as pain and dysesthesia. However, recent evidence suggest ROS can act on specific targets to induce physiological and pathological responses. In this study, we have shown that ROS-mediated activation of some ROS-sensitive TRP channels specifically contribute to the generation and prolongation of pain and dysesthesia. 1) TRPM2 mainly expressed on peripheral immune cells and spinal glial cells causes a wide range of pain mouse models, including inflammatory and neuropathic pain. 2) ROS-mediated activation of TRPA1, expressed on sensory neurons contributes to oxaliplatin-induced acute peripheral neuropathy and transient hindlimb ischemia/reperfusion-induced spontaneous dysesthesia, which are based to the inhibition of prolyl hydroxylase. 3) TRPA1 is involved in long-lasting cystitis model induced by intravesical injection of H2O2.

Free Research Field

薬理学