AUTHOR=Namer Barbara , Ørstavik Kirstin , Schmidt Roland , Mair Norbert , Kleggetveit Inge Petter , Zeidler Maximillian , Martha Theresa , Jorum Ellen , Schmelz Martin , Kalpachidou Theodora , Kress Michaela , Langeslag Michiel TITLE=Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype JOURNAL=Frontiers in Neurology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00335 DOI=10.3389/fneur.2017.00335 ISSN=1664-2295 ABSTRACT=

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.