ArticleAnnals of neurology2009
A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia.
Article in Annals of neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Pharmacotherapeutic Options for Managing Neuropathic Pain: A Systematic Review and Meta-Analysis.Pain research & management · 2021Pooled it
- The paraEuropean journal of pain (London, England) · 2026Article
- Article
- Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.Pediatric research · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Mepyramine targets mutant Nav1.7 channels to relieve pain and erythema in primary erythromelalgia patients.Frontiers in medicine · 2025Article
- Erythromelalgia caused by the missense mutation p.Arg220Pro in an alternatively spliced exon of SCN9A (NaV1.7).Human molecular genetics · 2024Article
- Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series.Children (Basel, Switzerland) · 2023Article
- Structural Conformation and Activity of Spider-Derived Inhibitory Cystine Knot Peptide Pn3a Are Modulated by pH.ACS omega · 2023Article
- Clinical Challenges in Primary Erythromelalgia: a Real-Life Experience from a Single Center and a Diagnostic-Therapeutic Flow-Chart Proposal.Dermatology practical & conceptual · 2023Article
- Structural mapping of NaNature communications · 2023Article
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
- Erythromelalgia: A Child With V400M Mutation in theNeurology. Genetics · 2021Article
- Status of peripheral sodium channel blockers for non-addictive pain treatment.Nature reviews. Neurology · 2020Review
- Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes.Scientific reports · 2020Article
- Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020Review
- Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7.The Journal of biological chemistry · 2020Article
- Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy.Brain : a journal of neurology · 2020Article
- Translational issues in precision medicine in neuropathic pain.Canadian journal of pain = Revue canadienne de la douleur · 2020Review
- Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveHuman and animal studies have shown that Na(v)1.7 sodium channels, which are preferentially expressed within nociceptors and sympathetic neurons, play a major role in inflammatory and neuropathic pain. Inherited erythromelalgia (IEM) has been linked to gain-of-function mutations of Na(v)1.7. We now report a novel mutation (V400M) in a three-generation Canadian family in which pain is relieved by carbamazepine (CBZ).
methodsWe extracted genomic DNA from blood samples of eight members of the family, and the sequence of SCN9A coding exons was compared with the reference Na(v)1.7 complementary DNA. Wild-type Na(v)1.7 and V400M cell lines were then analyzed using whole-cell patch-clamp recording for changes in activation, deactivation, steady-state inactivation, and ramp currents.
resultsWhole-cell patch-clamp studies of V400M demonstrate changes in activation, deactivation, steady-state inactivation, and ramp currents that can produce dorsal root ganglia neuron hyperexcitability that underlies pain in these patients. We show that CBZ, at concentrations in the human therapeutic range, normalizes the voltage dependence of activation and inactivation of this inherited erythromelalgia mutation in Na(v)1.7 but does not affect these parameters in wild-type Na(v)1.7.
interpretationOur results demonstrate a normalizing effect of CBZ on mutant Na(v)1.7 channels in this kindred with CBZ-responsive inherited erythromelalgia. The selective effect of CBZ on the mutant Na(v)1.7 channel appears to explain the ameliorative response to treatment in this kindred. Our results suggest that functional expression and pharmacological studies may provide mechanistic insights into hereditary painful disorders.
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