Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons

S. D. Dib-Hajj, A. M. Rush, Theodore Cummins, F. M. Hisama, S. Novella, L. Tyrrell, L. Marshall, S. G. Waxman

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

Erythromelalgia is an autosomal dominant disorder characterized by burning pain in response to warm stimuli or moderate exercise. We describe a novel mutation in a family with erythromelalgia in SCN9A, the gene that encodes the Nav 1.7 sodium channel. Nav1.7 produces threshold currents and is selectively expressed within sensory neurons including nociceptors. We demonstrate that this mutation, which produces a hyperpolarizing shift in activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single action potentials and high frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first inherited pain disorder in which it is possible to link a mutation with an abnormality in ion channel function and with altered firing of pain signalling neurons.

Original languageEnglish
Pages (from-to)1847-1854
Number of pages8
JournalBrain
Volume128
Issue number8
DOIs
StatePublished - Aug 2005

Fingerprint

Erythromelalgia
Sensory Receptor Cells
Mutation
Neurons
Pain
Nociceptors
Somatoform Disorders
Sodium Channels
Spinal Ganglia
Ion Channels
Action Potentials
Genes

Keywords

  • Channel
  • Channelopathy
  • Erythromelalgia
  • Mutation
  • Pain
  • Sodium

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dib-Hajj, S. D., Rush, A. M., Cummins, T., Hisama, F. M., Novella, S., Tyrrell, L., ... Waxman, S. G. (2005). Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain, 128(8), 1847-1854. https://doi.org/10.1093/brain/awh514

Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. / Dib-Hajj, S. D.; Rush, A. M.; Cummins, Theodore; Hisama, F. M.; Novella, S.; Tyrrell, L.; Marshall, L.; Waxman, S. G.

In: Brain, Vol. 128, No. 8, 08.2005, p. 1847-1854.

Research output: Contribution to journalArticle

Dib-Hajj, SD, Rush, AM, Cummins, T, Hisama, FM, Novella, S, Tyrrell, L, Marshall, L & Waxman, SG 2005, 'Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons', Brain, vol. 128, no. 8, pp. 1847-1854. https://doi.org/10.1093/brain/awh514
Dib-Hajj, S. D. ; Rush, A. M. ; Cummins, Theodore ; Hisama, F. M. ; Novella, S. ; Tyrrell, L. ; Marshall, L. ; Waxman, S. G. / Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. In: Brain. 2005 ; Vol. 128, No. 8. pp. 1847-1854.
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