期刊
NEUROSCIENCE LETTERS
卷 594, 期 -, 页码 163-168出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2015.01.084
关键词
Pain; Calcium imaging; Voltage-dependent Ca2+ channels; Fabry disease; Dorsal root ganglia
资金
- MRC
- Wellcome Trust
- BK21 programme
- EU IMI
- Wellcome Trust [101054/Z/13/Z] Funding Source: Wellcome Trust
- BBSRC [BB/F000227/1] Funding Source: UKRI
- MRC [G0901905] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F000227/1] Funding Source: researchfish
- Medical Research Council [G0901905] Funding Source: researchfish
- Wellcome Trust [101054/Z/13/Z] Funding Source: researchfish
Fabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphin-golipids, 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 100 nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1 mu M, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca2+ channels were substantially enhanced by application of 1 mu M 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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