ArticlePain2016
Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Role of EPAC1 in chronic pain.Biochemistry and biophysics reports · 2024Review
- Inhibition of CXCR2 as a therapeutic target for chronic post-surgical pain: Insights from animal and cell models.CytoJournal · 2024Article
- Bone marrow-derived mesenchymal stem cells attenuate complete Freund's adjuvant-induced inflammatory pain by inhibiting the expression of P2X3.Cell proliferation · 2023Article
- Suppression of P2X3 receptor-mediated currents by the activation of αCNS neuroscience & therapeutics · 2022Article
- Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Exchange proteins directly activated by cyclic adenosine monophosphate inhibitor reverses mechanical allodynia via the modification of astrocytes activity in the spinal cord.Annals of translational medicine · 2021Article
- Article
- 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
- Regulation of Mitochondrial Function by Epac2 Contributes to Acute Inflammatory Hyperalgesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Epac1 (Exchange Protein Directly Activated by cAMP 1) Upregulates LOX-1 (Oxidized Low-Density Lipoprotein Receptor 1) to Promote Foam Cell Formation and Atherosclerosis Development.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- P2X3 receptors contribute to transition from acute to chronic muscle pain.Purinergic signalling · 2020Article
- Antimycin A increases bronchopulmonary C-fiber excitability via protein kinase C alpha.Respiratory physiology & neurobiology · 2020Article
- βBritish journal of pharmacology · 2020Article
- Salusin-β mediates tubular cell apoptosis in acute kidney injury: Involvement of the PKC/ROS signaling pathway.Redox biology · 2020Article
- Effect of PKC/NF-Pain research & management · 2020Article
- Article
- Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression.International journal of molecular sciences · 2019Article
- Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.Neurobiology of disease · 2019Article
- Phospho-substrate profiling of Epac-dependent protein kinase C activity.Molecular and cellular biochemistry · 2019Article
- Role of p120 Catenin in Epac1-Induced Chronic Postsurgical Pain in Rats.Pain research & management · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)-dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses. On the other hand, the role of PKCα in receptor sensitization was seldom considered. Here, we studied the participation of PKCα in Epac signaling in P2X3R-mediated hyperalgesia. The expression of both Epac1 and Epac2 and the level of cAMP in DRGs are greatly enhanced after complete Freund adjuvant (CFA)-induced inflammation. The expression of phosphorylated PKCα is also upregulated. Complete Freund adjuvant (CFA)-induced P2X3R-mediated hyperalgesia is not only blocked by Epac antagonists but also by the classical PKC isoform inhibitors, Go6976, and PKCα-siRNA. These CFA effects are mimicked by the application of the Epac agonist, 8-(4-chlorophenylthio)-2 -O-methyl-cAMP (CPT), in control rats, further confirming the involvement of Epacs. Because the application of Go6976 prior to CPT still reduces CPT-induced hyperalgesia, PKCα is downstream of Epacs to mediate the enhancement of P2X3R responses in DRGs. The pattern of translocation of PKCα inside DRG neurons in response to CPT or CFA stimulation is distinct from that of PKCε. Thus, in contrast to prevalent view, PKCα also plays an essential role in producing complex inflammation-induced receptor-mediated 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.