Analysis to reveal the roles of TREK1 on cancer pain and to develop TREK1 agonists as novel analgesics for cancer patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Miyano Kanako 国立研究開発法人国立がん研究センター, 研究所, 研究員 (50597888)
• Co-Investigator(Kenkyū-buntansha): 上園 保仁 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: TREK1チャネル / オピオイド受容体 / TRPチャネル / 疼痛

Outline of Final Research Achievements

The aim of the present study was to reveal the roles of TREK1 on cancer pain and to develop TREK1 agonists as novel analgesics for cancer patients. We first constructed cells stably expressing opioid receptors (ORs), which were reported to activate TREK1. We next established cells expressing TREK1 and cells simultaneously expressing TREK1 and μOR. We then investigated effects of opioid analgesics on TREK1 activation and performed screenings of novel TREK1 using these cells.
In the mean time, we established a novel chemotherapy-induced neuropathic pain (CINP) mouse model using carboplatin, which showed enhanced TRPA1 activation via cAMP-PKA-AKAP pathway and induced mechanical and cold allodynia. Using this CINP model, investigation of involvement of TREK1 activities on neuropathic pain are ongoing.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

TREK1活性化剤は、TREK1を介した細胞内外のイオンバランス調整により疼痛および鎮痛の両面での神経活性を制御し、結果として鎮痛作用を発揮させるため、既存の鎮痛薬に比較し有効かつ副作用や耐性の生じにくい鎮痛薬となり得る。本研究は、難治性疼痛の克服によりがん患者のがん治療の継続を可能にすることで治療の完遂を促し、患者のQOL向上に寄与するだけでなく患者の生命予後の延長にも貢献すると考える。