Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
Department of Pain Medicine Research, Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
Methods Cell Biol. 2022;168:277-298. doi: 10.1016/bs.mcb.2021.12.019. Epub 2022 Jan 10.
While cancer patients may have chemotherapeutics to thank for being cured of their malignancy, they are often left to suffer a disabling neuropathy induced by that same cancer treatment. This neuropathy, known as chemotherapy-induced peripheral neuropathy, or CIPN, is one of the most debilitating survivorship concerns for patients, with many citing hallmark symptoms of hyperalgesia, allodynia, and numbness, and subsequently reducing their dose or even ceasing treatment altogether. Investigations into this interplay between the antineoplastic activity of chemotherapeutic agents and the preservation of peripheral nerve health are therefore crucial for the development of CIPN treatment and prevention methods. Responding to need, current literature is inundated with varying preclinical models of CIPN. This chapter thus seeks to provide a detailed and reliable methodology for the induction and assessment of CIPN in mice, using a preclinical model that is both reproducible and translatable to several aspects of the clinical phenotype. Specifically, this chapter lays out a model for intermittent low-dose paclitaxel induction of CIPN in C57BL/6J mice, and a testing of this induction via von Frey filament mechanical hypersensitivity assays, a mechanical hyposensitivity (numbness) assay, and a cold-thermal allodynia assay (acetone test). These protocols can easily be adjusted to fit the needs of individual CIPN experiments, as stated throughout the chapter.
虽然癌症患者可能因接受化疗而治愈恶性肿瘤,但他们往往会因同一癌症治疗而患上致残性周围神经病变。这种周围神经病变称为化疗诱导的周围神经病变(CIPN),是患者最致残的生存问题之一,许多患者出现痛觉过敏、感觉异常和麻木等标志性症状,从而减少剂量甚至完全停止治疗。因此,研究化疗药物的抗肿瘤活性与外周神经健康保护之间的相互作用对于开发 CIPN 治疗和预防方法至关重要。为了满足这一需求,目前的文献中充斥着各种 CIPN 的临床前模型。因此,本章旨在为使用可重现且可转化为临床表型多个方面的临床前模型,在小鼠中诱导和评估 CIPN 提供详细和可靠的方法。具体而言,本章提出了一种使用 C57BL/6J 小鼠间歇性低剂量紫杉醇诱导 CIPN 的模型,并通过 von Frey 细丝机械超敏反应测定、机械低敏性(麻木)测定和冷热感觉过敏测定(丙酮试验)来测试这种诱导。如本章所述,这些方案可以根据 CIPN 实验的具体需求进行调整。