Current Neurology and Neuroscience Reports

, Volume 12, Issue 1, pp 76–83

Pain Disorders and Erythromelalgia Caused by Voltage-Gated Sodium Channel Mutations

Nerve and Muscle (M Hirano and LH Weimer, Section Editors)

DOI: 10.1007/s11910-011-0233-8

Cite this article as:
Dabby, R. Curr Neurol Neurosci Rep (2012) 12: 76. doi:10.1007/s11910-011-0233-8


Voltage-gated sodium channels play a pivotal role in pain transmission. They are widely expressed in nociceptive neurons, and participate in the generation of action potentials. Alteration in ionic conduction of these channels causes abnormal electrical firing, thus renders neurons hyperexcitable. So far, mutations in the Nav1.7 sodium channel, which is expressed in the dorsal root ganglia cells and sympathetic neurons, have been described to cause perturbations in pain sensation. Until recently, gain-of-function Nav1.7 mutations were known to cause two neuropathic pain syndromes: inherited erythromelalgia and paroxysmal extreme pain syndrome. These syndromes are inherited in a dominant trait; they usually begin in childhood or infancy, and are characterized by attacks of severe neuropathic pain accompanied with autonomic symptoms. Recently, small fiber neuropathy and chronic nonparoxysmal pain have been described in patients harboring gain-of-function mutations in Nav1.7 channel. Loss-of-function mutations in Nav1.7 are extremely rare, and invariably cause congenital inability to perceive pain.


Sodium channels SCN9A gene Nav1.7 Inherited erythromelalgia Paroxysmal extreme pain disorder Small fiber neuropathy Neuropathic pain Congenital insensitivity to pain 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Neuromuscular Service, Department of NeurologyWolfson Medical CenterHolonIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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