Sensory TRP channels contribute differentially to skin inflammation and persistent itch.

Abstract

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.

• Authors: Jing Feng, Pu Yang, Madison R Mack, Dariia Dryn, Jialie Luo, Xuan Gong, Shenbin Liu, Landon K Oetjen, Alexander V Zholos, Zhinan Mei, Shijin Yin, Brian S Kim, Hongzhen Hu
• Journal: Nature communications (Nat Commun) Vol. 8 Issue 1 Pg. 980 (10 30 2017) ISSN: 2041-1723 [Electronic] England
• PMID: 29081531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• TRPA1 Cation Channel
• TRPV Cation Channels
• TRPV1 protein, mouse
• Trpa1 protein, mouse

Topics

• Animals
• Dermatitis, Allergic Contact (genetics, immunology)
• Disease Models, Animal
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Pruritus (genetics, immunology)
• Skin (immunology)
• TRPA1 Cation Channel (genetics, immunology)
• TRPV Cation Channels (genetics, immunology)