Familial pain syndromes from mutations of the Nav1.7 sodium channel

Authors

  • Tanya Z. Fischer,

    1. Department of Neurology
    2. Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, USA.
    3. Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut, USA
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  • Stephen G. Waxman

    1. Department of Neurology
    2. Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, USA.
    3. Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut, USA
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Address for correspondence: Stephen G. Waxman, M.D., Ph.D., Department of Neurology, LCI 707, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510. Voice: 203-785-6351; fax: 203-785-2238. stephen.waxman@yale.edu

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 (Nav1.7) 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 Nav1.7. Conversely, a loss-of-function of the Nav1.7 channel can produce channelopathy-associated insensitivity to pain. Therefore, the Nav1.7 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 Nav1.7 channel.

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