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MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sen...

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Autores principales: Lu, Ping, Zhao, Yonghui, Xie, Zili, Zhou, Huan, Dong, Xinzhong, Wu, Gregory F., Kim, Brian S., Feng, Jing, Hu, Hongzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514240/
https://www.ncbi.nlm.nih.gov/pubmed/36961815
http://dx.doi.org/10.1016/j.celrep.2023.112283
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author Lu, Ping
Zhao, Yonghui
Xie, Zili
Zhou, Huan
Dong, Xinzhong
Wu, Gregory F.
Kim, Brian S.
Feng, Jing
Hu, Hongzhen
author_facet Lu, Ping
Zhao, Yonghui
Xie, Zili
Zhou, Huan
Dong, Xinzhong
Wu, Gregory F.
Kim, Brian S.
Feng, Jing
Hu, Hongzhen
author_sort Lu, Ping
collection PubMed
description Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV1(+)/MrgprA3(+) prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin.
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spelling pubmed-105142402023-10-23 MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel Lu, Ping Zhao, Yonghui Xie, Zili Zhou, Huan Dong, Xinzhong Wu, Gregory F. Kim, Brian S. Feng, Jing Hu, Hongzhen Cell Rep Article Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV1(+)/MrgprA3(+) prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin. 2023-04-25 2023-03-22 /pmc/articles/PMC10514240/ /pubmed/36961815 http://dx.doi.org/10.1016/j.celrep.2023.112283 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Lu, Ping
Zhao, Yonghui
Xie, Zili
Zhou, Huan
Dong, Xinzhong
Wu, Gregory F.
Kim, Brian S.
Feng, Jing
Hu, Hongzhen
MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title_full MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title_fullStr MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title_full_unstemmed MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title_short MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
title_sort mrgpra3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive piezo2 channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514240/
https://www.ncbi.nlm.nih.gov/pubmed/36961815
http://dx.doi.org/10.1016/j.celrep.2023.112283
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