Department of Life Sciences and Health, Faculty of Health Sciences, Oslo Metropolitan University, 0130 Oslo, Norway.
Department of Health Science and Technology, Faculty of Medicine, Aalborg University, 9220 Aalborg East, Denmark.
Toxins (Basel). 2022 Oct 12;14(10):701. doi: 10.3390/toxins14100701.
Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined.
在报道肉毒杆菌神经毒素 (BoNTs) 具有止痒作用的二十年后，目前仍没有批准用于 BoNTs 止痒适应证的产品，大多数临床病例报告仍侧重于 BoNTs 治疗各种瘙痒症的超适应证使用。已经进行了一些随机临床试验，但结果存在争议，BoNTs 对抗瘙痒的有益作用主要基于病例研究和病例系列。这些研究在展示 BoNTs 在慢性瘙痒疾病中的潜在应用方面具有价值，但由于这些研究的性质，它们被归类为提供较低水平的证据或较低级别的推荐。为了获得 BoNTs 止痒适应证的批准，需要更高水平的证据，这可以通过进行大规模、精心设计的研究来实现，这些研究需要有适当的对照组，并建立可靠的、精心设计的主要和次要结局。除了临床证据外，展示 BoNTs 的基于机制的止痒作用可能会加强、加速和促进目前为进一步投资于该领域以加速 BoNTs 获得批准用于瘙痒症的努力。因此，本综述旨在从类似于瘙痒作为特征的各种临床情况的基础研究中，提供 BoNTs 止痒作用的最新机制。本文介绍了 BoNTs 调节神经元、神经胶质和免疫的作用，以减少瘙痒的传递的证据，并概述了未来的潜在方向。
