ArticleNeuroscience2015
Local knockdown of the NaV1.6 sodium channel reduces pain behaviors, sensory neuron excitability, and sympathetic sprouting in rat models of neuropathic pain.
Article in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Electrophysiological modulation of pain‑related sodium channels by cannabinoids: a systematic review.Journal of cannabis research · 2026Pooled it
- Contribution of proneurotrophin-3 to nerve trauma-induced neuropathic pain through promoting TrkC-mediated increase of CCL2 in primary sensory neurons.Brain, behavior, and immunity · 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
- TNF-α-preconditioning enhances analgesic efficacy of mesenchymal stem cell-derived extracellular vesicle in neuropathic painBioactive materials · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Small-molecule natural product sophoricoside reduces peripheral neuropathic pain via directly blocking of NaV1.6 in dorsal root ganglion nociceptive neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.ACS pharmacology & translational science · 2024Review
- Mineralocorticoid Receptor Antagonism Reduces Inflammatory Pain Measures in Mice Independent of the Receptors on Sensory Neurons.Neuroscience · 2024Article
- Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: Evidence for large primary afferents involvement in chronic pain.Experimental physiology · 2024Review
- Electrophysiological evaluation of the effect of peptide toxins on voltage-gated ion channels: a scoping review on theoretical and methodological aspects with focus on the Central and South American experience.The journal of venomous animals and toxins including tropical diseases · 2024Article
- Peripheral BDNF Regulates Somatosensory-Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain.Neuroscience bulletin · 2023Article
- A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression.Brain : a journal of neurology · 2023Article
- Exaptation and Evolutionary Adaptation in Nociceptor Mechanisms Driving Persistent Pain.Brain, behavior and evolution · 2023Review
- Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes.Frontiers in pharmacology · 2023Article
- Upregulation of NaCells · 2022Article
- Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.The journal of pain · 2022Article
- Chemical and Biological Tools for the Study of Voltage-Gated Sodium Channels in Electrogenesis and Nociception.Chembiochem : a European journal of chemical biology · 2022Review
- A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression.The Journal of clinical investigation · 2022Article
- Complex Regional Pain Syndrome: A Comprehensive Review.Pain and therapy · 2021Review
- Autistic-like behavior, spontaneous seizures, and increased neuronal excitability in a Scn8a mouse model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In the spinal nerve ligation (SNL) model of neuropathic pain, as in other pain models, abnormal spontaneous activity of myelinated sensory neurons occurs early and is essential for establishing pain behaviors and other pathologies. Sympathetic sprouting into the dorsal root ganglion (DRG) is observed after SNL, and sympathectomy reduces pain behavior. Sprouting and spontaneous activity may be mutually reinforcing: blocking neuronal activity reduces sympathetic sprouting, and sympathetic spouts functionally increase spontaneous activity in vitro. However, most studies in this field have used nonspecific methods to block spontaneous activity, methods that also block evoked and normal activity. In this study, we injected small inhibitory (si) RNA directed against the NaV1.6 sodium channel isoform into the DRG before SNL. This isoform can mediate high-frequency repetitive firing, like that seen in spontaneously active neurons. Local knockdown of NaV1.6 markedly reduced mechanical pain behaviors induced by SNL, reduced sympathetic sprouting into the ligated sensory ganglion, and blocked abnormal spontaneous activity and other measures of hyperexcitability in myelinated neurons in the ligated sensory ganglion. Immunohistochemical experiments showed that sympathetic sprouting preferentially targeted NaV1.6-positive neurons. Under these experimental conditions, NaV1.6 knockdown did not prevent or strongly alter single evoked action potentials, unlike previous less specific methods used to block spontaneous activity. NaV1.6 knockdown also reduced pain behaviors in another pain model, chronic constriction of the sciatic nerve, provided the model was modified so that the lesion site was relatively close to the siRNA-injected lumbar DRGs. The results highlight the relative importance of abnormal spontaneous activity in establishing both pain behaviors and sympathetic sprouting, and suggest that the NaV1.6 isoform may have value as a therapeutic target.
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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.