Waltz Tyler B, Burand Anthony J, Sadler Katelyn E, Stucky Cheryl L
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Neurobiol Pain. 2021 Sep 2;10:100074. doi: 10.1016/j.ynpai.2021.100074. eCollection 2021 Aug-Dec.
Fabry disease (FD) causes life-long pain, the mechanisms of which are unclear. Patients with FD have chronic pain that mirrors symptoms of other painful peripheral neuropathies. However, it is unclear what underlying damage occurs in FD peripheral nerves that may contribute to chronic pain. Here, we characterized myelinated and unmyelinated fiber pathology in peripheral nerves of a rat model of FD. Decreased nerve fiber density and increased nerve fiber pathology were noted in unmyelinated and myelinated fibers from FD rats; both observations were dependent on sampled nerve fiber modality and anatomical location. FD myelinated axons exhibited lipid accumulations that were determined to be the FD-associated lipid globotriaosylceramide (Gb3), and to a lesser extent lysosomes. These findings suggest that axonal Gb3 accumulation may drive peripheral neuron dysfunction and subsequent pain in FD.
法布里病（FD）会导致终身疼痛，其机制尚不清楚。FD患者的慢性疼痛与其他疼痛性周围神经病变的症状相似。然而，尚不清楚FD周围神经中发生了哪些潜在损伤可能导致慢性疼痛。在此，我们对FD大鼠模型的周围神经中有髓和无髓纤维病变进行了特征描述。在FD大鼠的无髓和有髓纤维中均观察到神经纤维密度降低和神经纤维病变增加；这两种观察结果均取决于所采样的神经纤维类型和解剖位置。FD有髓轴突表现出脂质蓄积，经测定为与FD相关的脂质球三糖神经酰胺（Gb3），在较小程度上还有溶酶体。这些发现表明，轴突Gb3蓄积可能导致FD外周神经元功能障碍及随后的疼痛。
