UMR INSERM 766, Clermont-Ferrand F-63001, France.
Neurotherapeutics. 2009 Oct;6(4):620-9. doi: 10.1016/j.nurt.2009.07.003.
This review examines recent preclinical research on toxic peripheral neuropathy and potential therapeutic developments. Chemotherapy-induced peripheral neurotoxicity is a major clinical problem because it represents the dose-limiting side effects of a significant number of antineoplastic drugs. Patients are unable to complete full or optimal treatment schedules. The incidence of chemotherapy-induced peripheral neuropathy varies depending on the drugs and schedules used, and this can be quite high, particularly when neurophysiological methods are used to make a diagnosis. However, even when chemotherapy-induced peripheral neuropathy is not a dose-limiting side effect, its onset may severely affect the quality of life of cancer patients and cause chronic discomfort. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity need for animal models is clinically relevant and will assist in the development of future neuroprotective strategies and also in the design of novel chemotherapies with improved toxicity profiles. In this review, the features of animal models of chemotherapy-induced painful neuropathy developed for 20 years, due to the administration of the most widely used drugs, such as platinum drugs, taxanes, and vinca alkaloids, will be discussed. In a second part, data available on neuroprotectants and treatment strategies, evaluated using these previous animal models in the attempt to prevent neuropathic pain, will be summarized.
这篇综述考察了最近关于毒理性周围神经病变的临床前研究和潜在的治疗进展。化疗引起的周围神经毒性是一个主要的临床问题,因为它代表了大量抗肿瘤药物的剂量限制副作用。患者无法完成完整或最佳的治疗方案。化疗引起的周围神经病变的发生率取决于所用药物和方案,这可能相当高,特别是当使用神经生理学方法进行诊断时。然而,即使化疗引起的周围神经病变不是剂量限制的副作用,其发作也可能严重影响癌症患者的生活质量,并导致慢性不适。因此,对化疗引起的神经毒性的病理生理学的更好理解需要动物模型,这在临床上是相关的,并将有助于开发未来的神经保护策略,以及设计具有改善毒性特征的新型化疗药物。在这篇综述中,将讨论由于最广泛使用的药物(如铂类药物、紫杉烷类和长春花生物碱)的给药而开发的用于 20 年的化疗引起的痛性周围神经病的动物模型的特征。在第二部分中,将总结使用这些先前的动物模型评估的神经保护剂和治疗策略的数据,试图预防神经病理性疼痛。