ArticleMolecular pain2011
Neuropathic Nav1.3-mediated sensitization to P2X activation is regulated by protein kinase C.
Article in Molecular pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- Effect of PKC/NF-Pain research & management · 2020Article
- Influence of intrathecal injection with dexmedetomidine on the behavioral ability and analgesic effects on rats with neuropathic pain and expression of protein kinase C in the spinal dorsal horn.Experimental and therapeutic medicine · 2018Article
- PKCβII-induced upregulation of PGP9.5 and VEGF in postoperative persistent pain in rats.Journal of pain research · 2018Article
- Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Brain natriuretic peptide constitutively downregulates P2X3 receptors by controlling their phosphorylation state and membrane localization.Molecular pain · 2015Article
- Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part I).Medical science monitor : international medical journal of experimental and clinical research · 2014Review
- The fundamental unit of pain is the cell.Pain · 2013Review
- Differential expression and pharmacology of native P2X receptors in rat and primate sensory neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice.The Journal of clinical investigation · 2012Article
- Tetrodotoxin (TTX) as a therapeutic agent for pain.Marine drugs · 2012Review
- In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization.Purinergic signalling · 2012Article
- Increased expression of sodium channel subunit Nav1.1 in the injured dorsal root ganglion after peripheral nerve injury.Anatomical record (Hoboken, N.J. : 2007) · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIncreased neuronal excitability and spontaneous firing are hallmark characteristics of injured sensory neurons. Changes in expression of various voltage-gated Na+ channels (VGSCs) have been observed under neuropathic conditions and there is evidence for the involvement of protein kinase C (PKC) in sensory hyperexcitability. Here we demonstrate the contribution of PKC to P2X-evoked VGSC activation in dorsal root ganglion (DRG) neurons in neuropathic conditions.
resultsUsing the spinal nerve ligation (SNL) model of neuropathic pain and whole-cell patch clamp recordings of dissociated DRG neurons, we examined changes in excitability of sensory neurons after nerve injury and observed that P2X3 purinoceptor-mediated currents induced by α,β-meATP triggered activation of TTX-sensitive VGSCs in neuropathic nociceptors only. Treatment of neuropathic DRGs with the PKC blocker staurosporine or calphostin C decreased the α,β-meATP-induced Na+ channels activity and reversed neuronal hypersensitivity. In current clamp mode, α,β-meATP was able to evoke action-potentials more frequently in neuropathic neurons than in controls. Pretreatment with calphostin C significantly decreased the proportion of sensitized neurons that generated action potentials in response to α,β-meATP. Recordings measuring VGSC activity in neuropathic neurons show significant change in amplitude and voltage dependence of sodium currents. In situ hybridization data indicate a dramatic increase in expression of embryonic Nav1.3 channels in neuropathic DRG neurons. In a CHO cell line stably expressing the Nav1.3 subunit, PKC inhibition caused both a significant shift in voltage-dependence of the channel in the depolarizing direction and a decrease in current amplitude.
conclusionNeuropathic injury causes primary sensory neurons to become hyperexcitable to ATP-evoked P2X receptor-mediated depolarization, a phenotypic switch sensitive to PKC modulation and mediated by increased activity of TTX-sensitive VGSCs. Upregulation in VGSC activity after injury is likely mediated by increased expression of the Nav1.3 subunit, and the function of the Nav1.3 channel is regulated by PKC.
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