The role of TRPA1 in cancer pain

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16493
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Yoshida Akari 和歌山県立医科大学, 医学部, 助教 (40584777)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: TRPA1 / がん性痛

Outline of Final Research Achievements

The purpose of this study was to examine the contribution of TRPA1 to cancer-induced pain by using a mouse model of cancer pain. Mice were subcutaneously injected a solution of Lewis lung carcinoma in the left plantar region. In a mouse model of cancer pain, the volumes of inoculated hind paws, spontaneous pain and mechanical and thermal hyperalgesia gradually increased throughout the observation period. Tumor growth and spontaneous pain were significantly suppressed in TRPA1 gene-deficient mice compared with wild-type mice. Mechanical and thermal hyperalgesia were comparable to wild-type mice. This study showed that TRPA1 is involved in tumor growth and spontaneous cancer pain-related behaviors but not in cancer induced mechanical and thermal hyperalgesia.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん性痛の末梢機序についてこれまで研究されていないTRPA1に注目した。結果、TRPA1遺伝子欠損マウスで作製した足底がん性痛モデルでは、野生型マウスと比較して腫瘍増殖および自発痛関連行動が有意に抑制されることが明らかとなった。TRPA1は主に末梢痛覚神経に発現しているため、TRPA1の機能抑制は中枢性の副作用のない鎮痛法開発につながる可能性が高い。TRPA1拮抗薬とオピオイドの併用により、オピオイドの投与量を減じても優れた鎮痛効果が得られ、かつ、オピオイドによる副作用を減じることが可能となりうる。これらはがん患者のQOL向上に大きく貢献すると考えられ、社会的意義は大きい。