Department of Anesthesiology, The Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine, St. Louis, MO, USA; Dermatology Hospital, Southern Medical University, Guangzhou, China.
Department of Anesthesiology, The Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine, St. Louis, MO, USA.
Cell Rep. 2023 Apr 25;42(4):112283. doi: 10.1016/j.celrep.2023.112283. Epub 2023 Mar 22.
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.
尽管触觉和瘙痒是由不同的神经元群体编码的，但轻度触摸也会在外源性瘙痒原存在的情况下引发瘙痒，从而产生一种称为 allo knesis 的现象。然而，瘙痒原诱导的机械性瘙痒敏化起始的细胞和分子机制尚不清楚。在这里，我们表明，组胺或氯喹 (CQ) 的皮内注射通过激活表达 TRPV1 和 MrgprA3 的瘙痒感受器引起 allo knesis，并且这些神经元的功能消融可逆转瘙痒原诱导的 allo knesis。此外，从表达 MrgprA3 的瘙痒感受器中遗传消融机械敏感的 Piezo2 通道功能也会抑制瘙痒原诱导的 allo knesis。在机制上，组胺和 CQ 通过激活磷脂酶 C (PLC) 和蛋白激酶 C-δ (PKCδ) 信号至少部分地敏化 Piezo2 通道功能。总之，我们的数据发现了 TRPV1/MrgprA3 瘙痒感受器-Piezo2 信号轴在皮肤中瘙痒原诱导的机械性瘙痒敏化的起始中的作用。
