マウスおいて硫化物の頬皮内投与により誘起される痒みと痛み：Cav3.2 T型カルシウムチャネル遺伝子欠失の影響

• Published in: 日本薬理学会年会要旨集 p. 3-P1-08
• Main Authors: 南野, 莉那, 川畑, 篤史, 西川, 裕之, 坪田, 真帆, 関口, 富美子, 倉橋, 翔太郎, 西山, 伊代
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: Ca2+ channel; itching; pain
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_3-P1-08

H2S, a gasotransmitter, is enzymatically formed from L-cysteine. We have reported that intraplantar injection of H2S donors, NaHS and Na2S, causes hyperalgesia/allodynia in mice, an effect abolished by genetic deletion of Cav3.2 among three isoforms of T-type Ca2+ channels (T-channels). Interestingly, their intradermal (i.d.) injection in mouse cheek simultaneously produces itch and pain, which are reduced by pharmacological blockade of T-channels. In the present study, we tested if distinct sulfides would induce itch and pain in the mouse cheek i.d. injection model, and examined the effect of Cav3.2 genetic deletion. The itch and pain responses, i.e. scratching with a hindlimb and wiping with a forelimb, respectively, were counted for 60 min following i.d. injection of test compounds in mice. Na2S and Na2S4 at 30-300 µg (0.38-3.8 and 0.17-1.7 µmol, respectively) as well as L-cysteine at 121-6050 µg (1-50 µmol) caused both scratching and wiping behaviors in a dose-dependent manner. The Na2S-induced scratching and wiping were abolished by TTA-A2, a selective T-channel blocker, and by genetic deletion of Cav3.2. Our study thus demonstrates that sulfides including L-cysteine as well as polysulfides participate in the T-channel-dependent itch and pain, and provides definitive evidence for the role of Cav3.2 in the sulfide-induced itch and pain.