Sensory TRP channels contribute differentially to skin inflammation and persistent itch

• Published in: Nature communications Vol. 8; no. 1; pp. 980 - 12
• Main Authors: Feng, Jing, Yang, Pu, Mack, Madison R., Dryn, Dariia, Luo, Jialie, Gong, Xuan, Liu, Shenbin, Oetjen, Landon K., Zholos, Alexander V., Mei, Zhinan, Yin, Shijin, Kim, Brian S., Hu, Hongzhen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2586; 631/378/340; 692/308/1426; Ablation; Capsaicin receptors; Channels; Contact dermatitis; Dermatitis; Excitability; Humanities and Social Sciences; Inflammation; Molecular modelling; multidisciplinary; Nerves; Pharmacology; Rodents; Science; Science (multidisciplinary); Scratching; Sensory neurons; Signal transduction; Signaling; Skin
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01056-8

Although both persistent itch and inflammation are commonly associated with allergic contact dermatitis (ACD), it is not known if they are mediated by shared or distinct signaling pathways. Here we show that both TRPA1 and TRPV1 channels are required for generating spontaneous scratching in a mouse model of ACD induced by squaric acid dibutylester (SADBE), a small molecule hapten, through directly promoting the excitability of pruriceptors. TRPV1 but not TRPA1 channels protect the skin inflammation, as genetic ablation of TRPV1 function or pharmacological ablation of TRPV1-positive sensory nerves promotes cutaneous inflammation in the SADBE-induced ACD. Our results demonstrate that persistent itch and inflammation are mediated by distinct cellular and molecular mechanisms in a mouse model of ACD. Identification of distinct roles of TRPA1 and TRPV1 in regulating itch and inflammation may provide new insights into the pathophysiology and treatment of chronic itch and inflammation in ACD patients. Allergic contact dermatitis is associated both with persistent itch and inflammation, but it is not known if these are mediated by shared signaling pathways. The authors show that persistent itch requires both TRPA1 and TRPV1, while TRPV1 has a protective role against skin inflammation in mice.