アロディニアを発症する担癌モデルマウスに対するジスルフィラムの鎮痛効果

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-104
• Main Authors: 藤塚, 亮次, 山田, 大輔, 寺島, 裕也, 林, 侑, 永井, 康晴, 太田, 有紗, 松浦, 航太, 斎藤, 顕宜, 松島, 綱治
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_1-B-P-104

Disulfiram (DSF), used as a treatment for alcoholism, has been found to have various points of action. We have reported that DSF exerts its anticancer effects by directly binding to and inhibiting the intracellular protein FROUNT, which promotes chemokine receptor CCR2 and CCR5 signaling expressed on macrophages (Nature Communications. 2020: 609). In addition, it has been reported that these chemokine receptor signals are deeply involved not only in "cancer" but also in "pain". In this study, we examined the analgesic effect of DSF by FROUNT inhibition in a new mouse model of carcinoma bearing allodynia.To create the carcinoma model, we subcutaneously transplanted a mouse lung cancer cell line, Lewis Lung Carcinoma (LLC), into the right back of mice. The mice developed a significant decrease in pain threshold in both legs about 2 weeks after transplantation. In addition, the number of CD11b-positive microglia, an activated microglial marker, were increased in the dorsal horn of the spinal cord. Next, to evaluate the analgesic effect, intraperitoneal administration of DSF significantly improved allodynia. Furthermore, this allodynia was significantly attenuated in FROUNT-deficient mice. These results suggest that DSF may be a useful therapeutic agent for cancer patients suffering from pain.