Familial pain syndromes from mutations of the NaV1.7 sodium channel

Ann N Y Acad Sci. 2010 Jan;1184:196-207. doi: 10.1111/j.1749-6632.2009.05110.x.

Abstract

The literature currently suggests that voltage-gated sodium channels play a major role in the pathogenesis of neuropathic pain. Alterations in the expression and targeting of specific sodium channels within injured dorsal root ganglia neurons appear to predispose the neurons to abnormal firing properties, allowing for the development of neuropathic pain. Mutations of one particular sodium channel (Na(v)1.7) have been shown to cause inherited neuropathic pain in humans, specifically in erythromelalgia and paroxysmal extreme pain disorder. Inherited erythromelalgia is the first human pain syndrome to be understood at a molecular level, having been linked to gain-of-function mutations of Na(v)1.7. Conversely, a loss-of-function of the Na(v)1.7 channel can produce channelopathy-associated insensitivity to pain. Therefore, the Na(v)1.7 channel may provide a unique target for the pharmacotherapy of pain in humans. In this review article we summarize current knowledge regarding several different disease manifestations arising from changes within the Na(v)1.7 channel.

Publication types

  • Review

MeSH terms

  • Action Potentials
  • Amino Acid Substitution
  • Animals
  • Chromosome Mapping
  • Erythromelalgia / genetics
  • Facial Neuralgia / genetics*
  • Facial Neuralgia / physiopathology
  • Ganglia, Spinal / physiopathology
  • Gene Expression Regulation
  • Humans
  • Mammals
  • Mutation
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neurons / physiology
  • Sodium Channels / genetics*
  • Sodium Channels / physiology

Substances

  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Sodium Channels