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A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels.
- Source :
-
Molecular pain [Mol Pain] 2016 Nov 07; Vol. 12. Date of Electronic Publication: 2016 Nov 07 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Small fiber neuropathy is a painful sensory nervous system disorder characterized by damage to unmyelinated C- and thinly myelinated Aδ- nerve fibers, clinically manifested by burning pain in the distal extremities and dysautonomia. The clinical onset in adulthood suggests a time-dependent process. The mechanisms that underlie nerve fiber injury in small fiber neuropathy are incompletely understood, although roles for energetic stress have been suggested. In the present study, we report time-dependent degeneration of neurites from dorsal root ganglia neurons in culture expressing small fiber neuropathy-associated G856D mutant Nav1.7 channels and demonstrate a time-dependent increase in intracellular calcium levels [Ca <superscript>2+</superscript> ] <subscript>i</subscript> and reactive oxygen species, together with a decrease in ATP levels. Together with a previous clinical report of burning pain in the feet and hands associated with reduced levels of Na <superscript>+</superscript> /K <superscript>+</superscript> -ATPase in humans with high altitude sickness, the present results link energetic stress and reactive oxygen species production with the development of a painful neuropathy that preferentially affects small-diameter axons.<br /> (© The Author(s) 2016.)
- Subjects :
- Animals
Cells, Cultured
Ganglia, Spinal cytology
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Humans
Luminescent Proteins genetics
Luminescent Proteins metabolism
Male
Nerve Degeneration genetics
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Time Factors
Transfection
Red Fluorescent Protein
Adenosine Triphosphate metabolism
Axons pathology
Calcium metabolism
Mutation genetics
NAV1.7 Voltage-Gated Sodium Channel genetics
Nerve Degeneration metabolism
Neurons cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8069
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular pain
- Publication Type :
- Academic Journal
- Accession number :
- 27821467
- Full Text :
- https://doi.org/10.1177/1744806916674472