School of Life Sciences, Henan University, Kaifeng 475001, China.
School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, D09 Dublin, Ireland.
Int J Mol Sci. 2022 Sep 1;23(17):9935. doi: 10.3390/ijms23179935.
Chronic itch is one of the most prominent clinical characteristics of diverse systematic diseases. It is a devastating sensation in pathological diseases. Despite its importance, there are no FDA-labelled drugs specifically geared toward chronic itch. The associated complex pathogenesis and diverse causes escalate chronic itch to being one of the top challenges in healthcare. Humanized antibodies against IL-13, IL-4, and IL-31 proved effective in treatment of itch-associated atopic dermatitis but remain to be validated in chronic itch. There are still no satisfactory anti-itch therapeutics available toward itch-related neuropeptides including GRP, BNP, SST, CGRP, and SP. The newly identified potential itch targets including OSM, NMB, glutamate, periostin, and Serpin E1 have opened new avenues for therapeutic development. Proof-of-principle studies have been successfully performed on antagonists against these proteins and their receptors in itch treatment in animal models. Their translational interventions in humans need to be evaluated. It is of great importance to summarize and compare the newly emerging knowledge on chronic itch and its pathways to promote the development of novel anti-itch therapeutics. The goal of this review is to analyze the different physiologies and pathophysiologies of itch mediators, whilst assessing their suitability as new targets and discussing future therapeutic development.
慢性瘙痒是多种系统性疾病的最显著临床特征之一。它是病理性疾病中一种令人痛苦的感觉。尽管它很重要，但目前还没有美国食品和药物管理局（FDA）批准的专门用于治疗慢性瘙痒的药物。相关的复杂发病机制和多种病因使得慢性瘙痒成为医疗保健领域的最大挑战之一。针对白细胞介素-13、白细胞介素-4 和白细胞介素-31 的人源化抗体已被证明可有效治疗瘙痒相关的特应性皮炎，但仍需在慢性瘙痒中验证。针对包括 GRP、BNP、SST、CGRP 和 SP 在内的与瘙痒相关的神经肽，目前仍没有令人满意的止痒治疗方法。新发现的潜在瘙痒靶点，包括 OSM、NMB、谷氨酸、骨膜蛋白和 Serpin E1，为治疗开发开辟了新途径。针对这些蛋白质及其在动物模型中的瘙痒受体的拮抗剂已在瘙痒治疗中成功进行了原理验证研究。需要对其在人类中的转化干预进行评估。总结和比较慢性瘙痒及其通路的新出现的知识对于促进新型止痒治疗方法的发展非常重要。本综述的目的是分析瘙痒介质的不同生理学和病理生理学，并评估它们作为新靶点的适用性，同时讨论未来的治疗发展。
