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.
Keywords: DRG, dorsal root ganglia; FD, Fabry disease; Fabry disease; Gb3, globotriaosylceramide; Globotriaosylceramide; IB4, isolectin B4; LAMP1, lysosomal-associated membrane protein 1; LM, Light microscopy; Lysosome; Nerve pathology; Neuropathic pain; TEM, transmission electron microscopy; α-GAL A, α-galactosidase A.
© 2021 Published by Elsevier Inc.