ArticleProceedings of the National Academy of Sciences of the United States of America2025
Nav1.8: Intrinsic limits on the functional effect of abrogation in DRG neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
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Who cites it
5 citing papers in PubMed.
- Deeper delving Nav1.8 inhibitor Suzetrigine in chronic pain.Acta pharmacologica Sinica · 2026Article
- Functional role of Nav1.8 channels in action potentials of mouse CGRP-lineage dorsal root ganglion neurons.The Journal of physiology · 2026Article
- Combinatorial logic of Nav channels in nociceptor excitability: Different degrees of synergy define distinct neuronal groups.bioRxiv : the preprint server for biology · 2026Article
- Mapping the Extended Pain Pathway: Human Genetic and Multi-Omic Strategies for Next-Generation Analgesics.International journal of molecular sciences · 2026Review
- Biophysical dissection of nociceptor hyperexcitability caused by a Nav1.8 gain-of-function mutation linked to severe pain.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Voltage-gated sodium channel Nav1.8 plays a crucial role in regulating excitability of small dorsal root ganglion (DRG) neurons and is an emerging target for pain therapeutics. Using dynamic clamp, we systematically manipulated Nav1.8 conductance to assess its impact on action potential (AP) electrogenesis, rheobase, and repetitive firing in native rat DRG neurons and those expressing the gain-of-function Nav1.7L858H mutation which underlies inherited erythromelalgia, a human genetic pain disorder. Our findings reveal that the Nav1.8 contribution to net sodium current is highly correlated with AP voltage threshold. Nav1.8 conductance regulated AP overshoot and voltage threshold without significantly affecting undershoot or resting membrane potential. We identified two populations of wild-type DRG neurons: strong responders (50% of cells), which exhibited substantial rheobase modulation with alterations in Nav1.8 conductance, and weak responders (50% of cells), which remained largely unaffected. In hyperexcitable Nav1.7L858H-expressing neurons, partial Nav1.8 subtraction (50%) restored rheobase above control levels in 63% of cells. However, weak responders (37%) remained hyperexcitable. The effect of Nav1.8 subtraction in responsive neurons supports the conclusion that Nav1.8 inhibition can reduce neuropathic pain. However, the presence of weakly responsive DRG neurons suggests that other channels might need to be targeted for full pain relief.
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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.