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

Harshvardhan Rolyan, Shujun Liu, Janneke G J Hoeijmakers, Catharina G. Faber, Ingemar S J Merkies, Giuseppe Lauria, Joel A. Black, Stephen G. Waxman

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 [Ca2+]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.

Original languageEnglish
JournalMolecular Pain
Volume12
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

Axons
Adenosine Triphosphate
Reactive Oxygen Species
Primary Dysautonomias
Altitude Sickness
Myelinated Nerve Fibers
Pain
Spinal Ganglia
Neurites
Nervous System Diseases
Nerve Fibers
Foot
Extremities
Hand
Calcium
Neurons
Wounds and Injuries
Small Fiber Neuropathy
Painful Neuropathy
sodium-translocating ATPase

Keywords

  • ATP
  • axon degeneration
  • mitochondria
  • peripheral neuropathy
  • reactive oxygen species
  • sodium-calcium exchanger
  • voltage-gated sodium channel

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Cite this

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. / Rolyan, Harshvardhan; Liu, Shujun; Hoeijmakers, Janneke G J; Faber, Catharina G.; Merkies, Ingemar S J; Lauria, Giuseppe; Black, Joel A.; Waxman, Stephen G.

In: Molecular Pain, Vol. 12, 01.10.2016.

Research output: Contribution to journalArticle

Rolyan, Harshvardhan ; Liu, Shujun ; Hoeijmakers, Janneke G J ; Faber, Catharina G. ; Merkies, Ingemar S J ; 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 Ca2+ dysregulation and decrease in ATP levels. In: Molecular Pain. 2016 ; Vol. 12.
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