Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina.
Mol Pain. 2021 Jan-Dec;17:17448069211033172. doi: 10.1177/17448069211033172.
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A (α-Gal A) activity which results in progressive accumulation of globotriaosylceramide (Gb3) and related metabolites. One prominent feature of Fabry disease is neuropathic pain. Accumulation of Gb3 has been documented in dorsal root ganglia (DRG) as well as other neurons, and has lately been associated with the mechanism of pain though the pathophysiology is still unclear. Small fiber (SF) neuropathy in FD differs from other entities in several aspects related to the perception of pain, alteration of fibers as well as drug therapies used in the practice with patients, with therapies far from satisfying. In order to develop better treatments, more information on the underlying mechanisms of pain is needed. Research in neuropathy has gained momentum from the development of preclinical models where different aspects of pain can be modelled and further analyzed. This review aims at describing the different in vitro and FD animal models that have been used so far, as well as some of the insights gained from their use. We focus especially in recent findings associated with ion channel alterations -that apart from the vascular alterations-, could provide targets for improved therapies in pain.
法布瑞氏病（FD）是一种渐进性的、X 连锁遗传性糖脂代谢紊乱疾病，由于溶酶体α-半乳糖苷酶 A（α-Gal A）活性缺乏或缺失，导致糖鞘脂（Gb3）和相关代谢物的逐渐积累。法布瑞氏病的一个显著特征是神经病理性疼痛。Gb3 的积累已在背根神经节（DRG）以及其他神经元中得到证实，最近与疼痛机制有关，尽管其病理生理学仍不清楚。FD 的小纤维（SF）神经病在几个方面与其他实体不同，与疼痛的感知、纤维的改变以及用于治疗患者的药物治疗有关，而这些治疗远未令人满意。为了开发更好的治疗方法，需要更多关于疼痛潜在机制的信息。神经病学的研究从临床前模型的发展中获得了动力，在这些模型中可以模拟和进一步分析疼痛的不同方面。这篇综述旨在描述迄今为止使用的不同体外和 FD 动物模型，以及从这些模型的使用中获得的一些见解。我们特别关注与离子通道改变相关的最新发现，这些改变除了血管改变外，还可能为疼痛的改善治疗提供靶点。
