ArticleBrain : a journal of neurology2020
Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Pharmacotherapeutic Options for Managing Neuropathic Pain: A Systematic Review and Meta-Analysis.Pain research & management · 2021Pooled it
- Targeting NaInternational journal of molecular sciences · 2026Review
- Article
- The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.The Journal of clinical investigation · 2025Article
- Correction of sodium channel mutations in sensory neurons reverses aberrant properties.Brain : a journal of neurology · 2025Article
- Targeting sodium channels - challenges for acute pain and the leap to chronic pain.Nature reviews. Neurology · 2025Review
- Inhibiting Nav1.8 for pain: Lessons from patients and from neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Discordance between preclinical and clinical testing of Na V 1.7-selective inhibitors for pain.Pain · 2025Review
- Mepyramine targets mutant Nav1.7 channels to relieve pain and erythema in primary erythromelalgia patients.Frontiers in medicine · 2025Article
- Integrative miRNA-mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy.Brain : a journal of neurology · 2023Article
- Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.International journal of molecular sciences · 2023Article
- Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors.Nature reviews. Neuroscience · 2023Review
- Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.Brain communications · 2023Article
- A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials.Journal of pain research · 2023Review
- Effective Modulation by Lacosamide on Cumulative Inhibition ofInternational journal of molecular sciences · 2022Article
- Small Fiber Neuropathy.Current pain and headache reports · 2022Review
- iPSCs and DRGs: stepping stones to new pain therapies.Trends in molecular medicine · 2022Review
- [Diagnostics and therapy of neuropathic pain].Der Anaesthesist · 2021Review
- Lacosamide Inhibition of NaFrontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Small fibre neuropathy is a common pain disorder, which in many cases fails to respond to treatment with existing medications. Gain-of-function mutations of voltage-gated sodium channel Nav1.7 underlie dorsal root ganglion neuronal hyperexcitability and pain in a subset of patients with small fibre neuropathy. Recent clinical studies have demonstrated that lacosamide, which blocks sodium channels in a use-dependent manner, attenuates pain in some patients with Nav1.7 mutations; however, only a subgroup of these patients responded to the drug. Here, we used voltage-clamp recordings to evaluate the effects of lacosamide on five Nav1.7 variants from patients who were responsive or non-responsive to treatment. We show that, at the clinically achievable concentration of 30 μM, lacosamide acts as a potent sodium channel inhibitor of Nav1.7 variants carried by responsive patients, via a hyperpolarizing shift of voltage-dependence of both fast and slow inactivation and enhancement of use-dependent inhibition. By contrast, the effects of lacosamide on slow inactivation and use-dependence in Nav1.7 variants from non-responsive patients were less robust. Importantly, we found that lacosamide selectively enhances fast inactivation only in variants from responders. Taken together, these findings begin to unravel biophysical underpinnings that contribute to responsiveness to lacosamide in patients with small fibre neuropathy carrying select Nav1.7 variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.