TY - JOUR
T1 - Sensory TRP channels contribute differentially to skin inflammation and persistent itch
AU - Feng, Jing
AU - Yang, Pu
AU - Mack, Madison R.
AU - Dryn, Dariia
AU - Luo, Jialie
AU - Gong, Xuan
AU - Liu, Shenbin
AU - Oetjen, Landon K.
AU - Zholos, Alexander V.
AU - Mei, Zhinan
AU - Yin, Shijin
AU - Kim, Brian S.
AU - Hu, Hongzhen
N1 - Funding Information:
This work was supported partly by grants from the National Institutes of Health, R01GM101218, R01DK103901 (to H.H.), and R01AR070116 (to B.S.K.), Washington University School of Medicine Digestive Disease Research Core Center (NIDDK P30 DK052574), The Center for the Study of Itch of Department of Anesthesiology at Washington University School of Medicine (to H.H.), and National Natural Science Foundation of China grant 81373379 (to S.Y.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85032494733&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01056-8
DO - 10.1038/s41467-017-01056-8
M3 - Article
C2 - 29081531
AN - SCOPUS:85032494733
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 980
ER -