ArticleThe Journal of general physiology2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain.
Article in The Journal of general physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- First-in-Human Phase I Trial of HRS-2129, a Selective Nav1.8 Inhibitor: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects.Drug design, development and therapy · 2026Trial
- Deeper delving Nav1.8 inhibitor Suzetrigine in chronic pain.Acta pharmacologica Sinica · 2026Article
- Comparative Electrophysiological Analysis of Trigeminal and Dorsal Root Ganglion Neurons in Mice.eNeuro · 2026Article
- Muscle-Nerve Signaling and Neurogenic Inflammation in Temporomandibular Disorders: Potential Contributions of Occlusal Interference and Other Peripheral Triggers.Dentistry journal · 2026Review
- Functional role of Nav1.8 channels in action potentials of mouse CGRP-lineage dorsal root ganglion neurons.The Journal of physiology · 2026Article
- Targeting Supramolecular Active Complexes of NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Combinatorial logic of Nav channels in nociceptor excitability: Different degrees of synergy define distinct neuronal groups.bioRxiv : the preprint server for biology · 2026Article
- The Excelsatoxin A-Receptor TMEM233 Modulates Nav1.8.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cartilage targeting hydrogel nanoplatform degrades BRD4 to alleviate osteoarthritis via Nav1.7 axis.Nature communications · 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
- Review of Physiology, Pathology, and Pharmacology of Voltage-Gated Sodium Channels in Regards to the Potential Role of NaV 1.8 Selective Inhibitor, Suzetrigine, for Chronic Pain Management.Journal of pain research · 2026Review
- Manual Massage Therapy for Neuropathic Pain: Clinical Evidence and Mechanistic Insights.Pain research & management · 2026Review
- Electroactive biomaterials modulating ion channels in nervous system regeneration.Regenerative biomaterials · 2026Review
- Neuroinflammation-Modulating Properties Combining Glutathione, N-Acetylcysteine, and Uridine Monophosphate in a Formulation Supplement: An In Vitro Study.Brain sciences · 2025Article
- Decoding orofacial pain: a translational review of mechanisms and novel therapies.The journal of headache and pain · 2025Review
- Targeting sodium channels - challenges for acute pain and the leap to chronic pain.Nature reviews. Neurology · 2025Review
- Nav1.8: Intrinsic limits on the functional effect of abrogation in DRG neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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
- An approach to targeting Nav1.7 for pain sensations.The Journal of clinical investigation · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
While voltage-gated sodium channels Nav1.7 and Nav1.8 both contribute to electrogenesis in dorsal root ganglion (DRG) neurons, details of their interactions have remained unexplored. Here, we studied the functional contribution of Nav1.8 in DRG neurons using a dynamic clamp to express Nav1.7L848H, a gain-of-function Nav1.7 mutation that causes inherited erythromelalgia (IEM), a human genetic model of neuropathic pain, and demonstrate a profound functional interaction of Nav1.8 with Nav1.7 close to the threshold for AP generation. At the voltage threshold of -21.9 mV, we observed that Nav1.8 channel open-probability exceeded Nav1.7WT channel open-probability ninefold. Using a kinetic model of Nav1.8, we showed that a reduction of Nav1.8 current by even 25-50% increases rheobase and reduces firing probability in small DRG neurons expressing Nav1.7L848H. Nav1.8 subtraction also reduces the amplitudes of subthreshold membrane potential oscillations in these cells. Our results show that within DRG neurons that express peripheral sodium channel Nav1.7, the Nav1.8 channel amplifies excitability at a broad range of membrane voltages with a predominant effect close to the AP voltage threshold, while Nav1.7 plays a major role at voltages closer to resting membrane potential. Our data show that dynamic-clamp reduction of Nav1.8 conductance by 25-50% can reverse hyperexcitability of DRG neurons expressing a gain-of-function Nav1.7 mutation that causes pain in humans and suggests, more generally, that full inhibition of Nav1.8 may not be required for relief of pain due to DRG neuron hyperexcitability.
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Registered trials
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