ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Small-fiber neuropathy Nav1.8 mutation shifts activation to hyperpolarized potentials and increases excitability of dorsal root ganglion neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 125 citations in OpenAlex.
- A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective NaClinical and translational science · 2022Trial
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults.Pain medicine (Malden, Mass.) · 2021Trial
- A neurocutaneous NaScience advances · 2026Article
- Targeting Supramolecular Active Complexes of NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- NaBrain communications · 2026Article
- Targeting sodium channels - challenges for acute pain and the leap to chronic pain.Nature reviews. Neurology · 2025Review
- Proton Density of the Dorsal Root Ganglia in Classical Fabry Disease: MRI Correlates of Small Fibre Neuropathy.Biomedicines · 2025Article
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Human sensory neurons exhibit cell-type-specific, pain-associated differences in intrinsic excitability and expression ofbioRxiv : the preprint server for biology · 2025Article
- Article
- Structural basis of inhibition of human NaNature communications · 2025Article
- Structural basis of inhibition of human NabioRxiv : the preprint server for biology · 2024Article
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a functional assessment.Stem cell research & therapy · 2024Article
- Studying serum neurofilament light chain levels as a potential new biomarker for small fiber neuropathy.European journal of neurology · 2024Article
- Computational modeling to study the impact of changes in Nav1.8 sodium channel on neuropathic pain.Frontiers in computational neuroscience · 2024Article
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a comparison of two protocols.Research square · 2023Article
- Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic small-fiber neuropathy (I-SFN), clinically characterized by burning pain in distal extremities and autonomic dysfunction, is a disorder of small-caliber nerve fibers of unknown etiology with limited treatment options. Functional variants of voltage-gated sodium channel Nav1.7, encoded by SCN9A, have been identified in approximately one-third of I-SFN patients. These variants render dorsal root ganglion (DRG) neurons hyperexcitable. Sodium channel Nav1.8, encoded by SCN10A, is preferentially expressed in small-diameter DRG neurons, and produces most of the current underlying the upstroke of action potentials in these neurons. We previously demonstrated two functional variants of Nav1.8 that either enhance ramp current or shift activation in a hyperpolarizing direction, and render DRG neurons hyperexcitable, in I-SFN patients with no mutations of SCN9A. We have now evaluated additional I-SFN patients with no mutations in SCN9A, and report a novel I-SFN-related Nav1.8 mutation I1706V in a patient with painful I-SFN. Whole-cell voltage-clamp recordings in small DRG neurons demonstrate that the mutation hyperpolarizes activation and the response to slow ramp depolarizations. However, it decreases fractional channels resistant to fast inactivation and reduces persistent currents. Current-clamp studies reveal that mutant channels decrease current threshold and increase the firing frequency of evoked action potentials within small DRG neurons. These observations suggest that the effects of this mutation on activation and ramp current are dominant over the reduced persistent current, and show that these pro-excitatory gating changes confer hyperexcitability on peripheral sensory neurons, which may contribute to pain in this individual with I-SFN.
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