title: Painful peripheral neuropathy and sodium channel mutations.
abstract: Peripheral neuropathy can lead to neuropathic pain in a subset of patients. Painful peripheral neuropathy is a debilitating disorder, reflected by a reduced quality of life. Therapeutic strategies are limited and often disappointing, as in most cases targeted treatment is not available. Elucidating pathogenetic factors for pain might provide a target for optimal treatment. Voltage-gated sodium channels NaV1.7-NaV1.9 are expressed in the small-diameter dorsal root ganglion neurons and their axons. By a targeted gene approach, missense gain-of-function mutations of NaV1.7-NaV1.9 have been demonstrated in painful peripheral neuropathy. Functional analyses have shown that these mutations produce a spectrum of pro-excitatory changes in channel biophysics, with the shared outcome at the cellular level of dorsal root ganglion hyperexcitability. Reduced neurite outgrowth may be another consequence of sodium channel mutations, and possible therapeutic strategies include blockade of sodium channels or block of reverse operation of the sodium-calcium exchanger. Increased understanding of the pathophysiology of painful peripheral neuropathy offers new targets that may provide a basis for more effective treatment.
authors.affiliation: Department of Neurology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. Electronic address: j.hoeijmakers@mumc.nl.
authors.forename: Janneke G J
authors.initials: JG
authors.lastname: Hoeijmakers
authors.affiliation: Department of Neurology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. Electronic address: c.faber@mumc.nl.
authors.forename: Catharina G
authors.initials: CG
authors.lastname: Faber
authors.affiliation: Department of Neurology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands; Department of Neurology, Spaarne Hospital, 2130 AT Hoofddorp, The Netherlands. Electronic address: isjmerkies@planet.nl.
authors.forename: Ingemar S J
authors.initials: IS
authors.lastname: Merkies
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06515, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT 06515, USA. Electronic address: stephen.waxman@yale.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D001369:Axons / Q000473:pathology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D009437:Neuralgia / Q000235:genetics* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D061566:Voltage-Gated Sodium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Painful peripheral neuropathy; Small-fiber neuropathy; Voltage-gated sodium channels