ArticlePain2019
The role of Nav1.7 in human nociceptors: insights from human induced pluripotent stem cell-derived sensory neurons of erythromelalgia patients.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04835779 (Biometric and Biological Data for Diagnosis and Therapy of Pain Patients German), which is not on this map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Biometric and Biological Data for Diagnosis and Therapy of Pain Patients German: Biometrische Und Biologische Daten für Die Diagnose Und Therapie Bei Schmerzpatienten
Who cites it
54 citing papers in PubMed.
- Rapid generation of human sensory neurons from iPSC for modeling of peripheral neuropathies.Journal of neuroscience methods · 2026Article
- Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes.Neural regeneration research · 2026Article
- Muscle-Nerve Signaling and Neurogenic Inflammation in Temporomandibular Disorders: Potential Contributions of Occlusal Interference and Other Peripheral Triggers.Dentistry journal · 2026Review
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- [N-Check: nerve check to document chemotherapy-induced peripheral neuropathy (CIPN) in incurable cancer].Schmerz (Berlin, 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
- Article
- Decoding Pain: Next-Generation In Vitro Systems for Mechanistic Insights and Drug Discovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Screening of candidate analgesics using a patient-derived human iPSC model of nociception identifies putative compounds for therapeutic treatment.Clinical and translational medicine · 2025Article
- Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.The Journal of general physiology · 2025Article
- Sodium channels as a new target for pain treatment.Frontiers in pharmacology · 2025Review
- Discovery of E0199: A novel compound targeting both peripheral NaJournal of pharmaceutical analysis · 2025Article
- Calcium-sensing receptor regulates Kv7 channels via GBritish journal of pharmacology · 2024Article
- Electrophysiological Analyses of Human Dorsal Root Ganglia and Human Induced Pluripotent Stem Cell-derived Sensory Neurons From Male and Female Donors.The journal of pain · 2024Article
- The pain target NaPflugers Archiv : European journal of physiology · 2024Article
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a functional assessment.Stem cell research & therapy · 2024Article
- Phenotypic Screening of Prospective Analgesics Among FDA-Approved Compounds using an iPSC-Based Model of Acute and Chronic Inflammatory Nociception.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a comparison of two protocols.Research square · 2023Article
- Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner.Advanced healthcare materials · 2023Article
- Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability.Brain : a journal of neurology · 2023Article
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (NaV) 1.7. Still, recent studies targeting NaV1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells from IEM patients with the NaV1.7/I848T mutation into sensory nociceptors. Action potentials in these IEM nociceptors displayed a decreased firing threshold, an enhanced upstroke, and afterhyperpolarization, all of which may explain the increased pain experienced by patients. Subsequently, we investigated the voltage dependence of the tetrodotoxin-sensitive NaV activation in these human sensory neurons using a specific prepulse voltage protocol. The IEM mutation induced a hyperpolarizing shift of NaV activation, which leads to activation of NaV1.7 at more negative potentials. Our results indicate that NaV1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with induced pluripotent stem cell-derived sensory neurons provides a new rationale for NaV1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.
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Registered trials
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