ArticleThe Journal of clinical investigation2012
PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
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- Neuronal activity-induced GLUT3 plasma translocation supports energy demands for memory acquisition.Communications biology · 2025Article
- Brain-specific serine/threonine-protein kinase 1 is a substrate of protein kinase C epsilon involved in sex-specific ethanol and anxiety phenotypes.Addiction biology · 2024Article
- Therapeutic Potential of Combinative shRNA-Encoded Lentivirus-Mediated Gene Silencing to Accelerate Somatosensory Recovery After Spinal Cord Trauma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Predictive analytics identifies key factors driving hyperalgesic priming of muscle sensory neurons.Frontiers in neuroscience · 2023Article
- Identification of key factors driving inflammation-induced sensitization of muscle sensory neurons.Frontiers in neuroscience · 2023Article
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- Activation of PKCε-ALDH2 Axis Prevents 4-HNE-Induced Pain in Mice.Biomolecules · 2021Article
- Oxidative stress induced by NOX2 contributes to neuropathic pain via plasma membrane translocation of PKCε in rat dorsal root ganglion neurons.Journal of neuroinflammation · 2021Article
- Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.Nature communications · 2021Article
- Antimycin A increases bronchopulmonary C-fiber excitability via protein kinase C alpha.Respiratory physiology & neurobiology · 2020Article
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- Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia.Journal of pain research · 2020Article
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- Preventive action of benztropine on platinum-induced peripheral neuropathies and tumor growth.Acta neuropathologica communications · 2019Article
- Reducing inflammation through delivery of lentivirus encoding for anti-inflammatory cytokines attenuates neuropathic pain after spinal cord injury.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanical hyperalgesia is a common and potentially disabling complication of many inflammatory and neuropathic conditions. Activation of the enzyme PKCε in primary afferent nociceptors is a major mechanism that underlies mechanical hyperalgesia, but the PKCε substrates involved downstream are not known. Here, we report that in a proteomic screen we identified the NaV1.8 sodium channel, which is selectively expressed in nociceptors, as a PKCε substrate. PKCε-mediated phosphorylation increased NaV1.8 currents, lowered the threshold voltage for activation, and produced a depolarizing shift in inactivation in wild-type - but not in PKCε-null - sensory neurons. PKCε phosphorylated NaV1.8 at S1452, and alanine substitution at this site blocked PKCε modulation of channel properties. Moreover, a specific PKCε activator peptide, ψεRACK, produced mechanical hyperalgesia in wild-type mice but not in Scn10a-/- mice, which lack NaV1.8 channels. These studies demonstrate that NaV1.8 is an important, direct substrate of PKCε that mediates PKCε-dependent mechanical hyperalgesia.
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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.