Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein–coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.

瘙痒的发病机制广泛表征为组胺能和非组胺能途径，并通过 2 个主要受体家族传播：G 蛋白偶联受体和瞬时受体电位通道。在皮肤中，瘙痒主要通过无髓 C 型和薄髓 A 型神经纤维传播。免疫系统和神经系统之间的串扰调节皮肤、脊髓和大脑的瘙痒传播。在许多已知的瘙痒原中，Th2 细胞因子，例如白细胞介素 4、白细胞介素 13、白细胞介素 31 和胸腺基质淋巴细胞生成素，是通过共享 Janus 激酶途径发出信号的特别重要的介质，代表了新型瘙痒治疗的新靶点。新出现的证据还表明，阿片能系统是一种有效的瘙痒传播调节剂，μ-阿片类药物活性增加和 κ-阿片类药物活性降低导致瘙痒发病机制。瘙痒的最佳管理需要针对特定​​的病因瘙痒亚型量身定制治疗方法。当病因不明且患者被诊断为来源不明的慢性瘙痒时，治疗应以 Th2 极化的存在为指导，通常表现为血嗜酸性粒细胞增加。在这个 2 部分系列的第二篇文章中，我们概述了我们目前对瘙痒发病机制的理解，并讨论了可用的和新兴的瘙痒治疗方法。治疗应以 Th2 极化的存在为指导，通常表现为血嗜酸性粒细胞增加。在这个 2 部分系列的第二篇文章中，我们概述了我们目前对瘙痒发病机制的理解，并讨论了可用的和新兴的瘙痒治疗方法。治疗应以 Th2 极化的存在为指导，通常表现为血嗜酸性粒细胞增加。在这个 2 部分系列的第二篇文章中，我们概述了我们目前对瘙痒发病机制的理解，并讨论了可用的和新兴的瘙痒治疗方法。