The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla-/0). The skin innervation of Gla-/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla-/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla-/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla-/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.
Keywords: Fabry disease; electrophysiology; lysosomal storage disorder; neuronal excitability; nociception; single fiber recordings.