虽然触摸和瘙痒是由不同的神经元群体编码的,轻微的触摸也会引起瘙痒,在存在外源性瘙痒,导致了一种叫做同构的现象。然而,对引发瘙痒原引起的机械瘙痒致敏的细胞和分子机制了解甚少。这里,我们显示,皮内注射组胺或氯喹(CQ)通过激活表达TRPV1-和MrgprA3的瘙痒受体来引起同种异体,这些神经元的功能消融逆转了pruritogen诱导的异常。此外,表达MrgprA3的瘙痒感受器对机械敏感性Piezo2通道功能的遗传消融也会抑制瘙痒原诱导的异常。机械上,组胺和CQ使Piezo2通道功能敏感,至少在某种程度上,通过激活磷脂酶C(PLC)和蛋白激酶C-δ(PKCδ)信号。总的来说,我们的数据发现TRPV1+/MrgprA3+瘙痒感受器-Piezo2信号轴在引发瘙痒原诱导的皮肤机械性瘙痒致敏时出现.
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.