The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain

Neurosci Lett. 2015 May 6:594:163-8. doi: 10.1016/j.neulet.2015.01.084. Epub 2015 Feb 16.


Fabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphingolipids, and accompanied by clinical manifestations, such as cardiac disorders, renal failure, pain and peripheral neuropathy. Globotriaosylsphingosine (lyso-Gb3), a deacylated form of globotriaosylceramide (Gb3), has emerged as a marker of Fabry disease. We investigated the link between Gb3, lyso-Gb3 and pain. Plantar administration of lyso-Gb3 or Gb3 caused mechanical allodynia in healthy mice. In vitro application of 100nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1μM, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca(2+) channels were substantially enhanced by application of 1μM lyso-Gb3. These studies suggest a direct role for lyso-Gb3 in the sensitisation of peripheral nociceptive neurons that may provide an opportunity for therapeutic intervention in the treatment of Fabry disease-associated pain.

Keywords: Calcium imaging; Dorsal root ganglia; Fabry disease; Pain; Voltage-dependent Ca(2+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / physiology*
  • Cells, Cultured
  • Fabry Disease / metabolism*
  • Fabry Disease / physiopathology
  • Ganglia, Spinal / cytology
  • Glycolipids / metabolism
  • Glycolipids / pharmacology*
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Mice, Inbred C57BL
  • Nociceptors / drug effects*
  • Nociceptors / physiology
  • Pain / metabolism*
  • Pain / physiopathology
  • Physical Stimulation
  • Sphingolipids / metabolism
  • Sphingolipids / pharmacology*
  • Touch
  • Trihexosylceramides / metabolism
  • Trihexosylceramides / pharmacology


  • Calcium Channels
  • Glycolipids
  • Sphingolipids
  • Trihexosylceramides
  • globotriaosyl lysosphingolipid
  • globotriaosylceramide
  • Calcium