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

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

Research output: Contribution to journalArticle

312 Scopus citations

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 (US)
Pages (from-to)1847-1854
Number of pages8
JournalBrain
Volume128
Issue number8
DOIs
StatePublished - Aug 1 2005

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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    Dib-Hajj, S. D., Rush, A. M., Cummins, T. R., Hisama, F. M., Novella, S., Tyrrell, L., Marshall, 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