Elucidation of oxaliplatin-induced peripheral neuropathy focusing on peripheral blood flow / peripheral temperature regulation mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22706
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kyoto University
• Principal Investigator: Ogihara Takashi 京都大学, 薬学研究科, 特定助教 (00883612)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: オキサリプラチン / 末梢神経障害 / 末梢血流障害 / 疼痛モデル

Outline of Final Research Achievements

Oxaliplatin (L-OHP), a platinum-based chemotherapeutic drug used as first line chemotherapy, induces peripheral neuropathy. So far, it has been clarified that peripheral blood flow dysfunction induced by L-OHP is involved in the development of peripheral neuropathy. In this study, we focused on the functional relationship between sensory nerves and blood vessels, and clarified that L-OHP causes abnormalities in sensory nerve vascular responses. Our results suggest that L-OHP not only directly damages peripheral nerves, but also causes abnormalities in vascular responsiveness due to sensory nerves, which leads to decreased peripheral blood flow and exacerbation of peripheral neuropathy. It is suggested that abnormalities in the peripheral sensory nerve-vascular relationship are involved in peripheral neuropathy.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

がん化学療法で用いられる抗がん剤は、様々な副作用が出現するが、なかでも末梢神経障害は、比較的多くの患者が経験するにもかかわらず、対応が遅れている副作用の１つである。末梢神経障害は、しびれ、感覚障害、痛みなどの感覚異常が生じ、患者の日常生活動作や生活の質を低下させる。さらには、重症化すれば、抗がん剤の減量や休薬を余儀なくさせ、がん治療成績に影響を与えることもあるが、その詳細な機序は不明な点が多い。今回得られた研究成果は末梢神経障害の発症機序の一部を解明したものであり、新たな予防/治療法の開発へとつながるものである。