TY - JOUR
T1 - Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle
AU - Feng, Jing
AU - Zhao, Yonghui
AU - Xie, Zili
AU - Zang, Kaikai
AU - Sviben, Sanja
AU - Hu, Xueming
AU - Fitzpatrick, James A.J.
AU - Wen, Lu
AU - Liu, Yifei
AU - Wang, Ting
AU - Lawson, Katy
AU - Liu, Qin
AU - Yan, Yan
AU - Dong, Xinzhong
AU - Han, Liang
AU - Wu, Gregory F.
AU - Kim, Brian S.
AU - Hu, Hongzhen
N1 - Funding Information:
We thank S. M. Carlton, A. Beyder, and R. Hill for helpful discussion. Atoh1CreERT mouse line was provided by M. Hoshinoa, E. A. Lumpkin, and B. U. Hoffman. Atoh1f/f mouse line was provided by N. F. Shroyer and R. D. Newberry. Q.L. is also affiliated with Departments of Ophthalmology and Visual Sciences and Neuroscience of Washington University School of Medicine. This study did not generate new unique reagents.This work was supported by NIH grant R01AA027065 to H.H. (NINDS), NIH grant R01AR077183 to H.H. (NIAMS). NIH grant R01DK103901 to H.H. (NIDDK), NIH grant R01NS106289 to G.F.W. (NINDS), The Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital grant CDI-CORE-2015-505 to J.A.J.F., The Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital grant CDI-CORE-2019-813 to J.A.J.F., and The Foundation for Barnes-Jewish Hospital grant 3770 to J.A.J.F.
Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved.
PY - 2022/7/13
Y1 - 2022/7/13
N2 - Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3+ pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.
AB - Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3+ pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.
UR - http://www.scopus.com/inward/record.url?scp=85134854415&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abn4819
DO - 10.1126/scitranslmed.abn4819
M3 - Article
C2 - 35857641
AN - SCOPUS:85134854415
SN - 1946-6234
VL - 14
JO - Science translational medicine
JF - Science translational medicine
IS - 653
M1 - eabn4819
ER -