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A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels

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....

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Autores principales: Rolyan, Harshvardhan, Liu, Shujun, Hoeijmakers, Janneke GJ, Faber, Catharina G, Merkies, Ingemar SJ, Lauria, Giuseppe, Black, Joel A, Waxman, Stephen G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102167/
https://www.ncbi.nlm.nih.gov/pubmed/27821467
http://dx.doi.org/10.1177/1744806916674472
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author Rolyan, Harshvardhan
Liu, Shujun
Hoeijmakers, Janneke GJ
Faber, Catharina G
Merkies, Ingemar SJ
Lauria, Giuseppe
Black, Joel A
Waxman, Stephen G
author_facet Rolyan, Harshvardhan
Liu, Shujun
Hoeijmakers, Janneke GJ
Faber, Catharina G
Merkies, Ingemar SJ
Lauria, Giuseppe
Black, Joel A
Waxman, Stephen G
author_sort Rolyan, Harshvardhan
collection PubMed
description 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(2+)](i) 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(+)/K(+)-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.
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spelling pubmed-51021672016-11-18 A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels Rolyan, Harshvardhan Liu, Shujun Hoeijmakers, Janneke GJ Faber, Catharina G Merkies, Ingemar SJ Lauria, Giuseppe Black, Joel A Waxman, Stephen G Mol Pain Research Article 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(2+)](i) 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(+)/K(+)-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. SAGE Publications 2016-11-07 /pmc/articles/PMC5102167/ /pubmed/27821467 http://dx.doi.org/10.1177/1744806916674472 Text en © The Author(s) 2016 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Rolyan, Harshvardhan
Liu, Shujun
Hoeijmakers, Janneke GJ
Faber, Catharina G
Merkies, Ingemar SJ
Lauria, Giuseppe
Black, Joel A
Waxman, Stephen G
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title_full A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title_fullStr A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title_full_unstemmed A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title_short A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca(2+) dysregulation and decrease in ATP levels
title_sort painful neuropathy-associated nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular ca(2+) dysregulation and decrease in atp levels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102167/
https://www.ncbi.nlm.nih.gov/pubmed/27821467
http://dx.doi.org/10.1177/1744806916674472
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