ArticleProceedings of the National Academy of Sciences of the United States of America2013
Neuronal prostaglandin E2 receptor subtype EP3 mediates antinociception during inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Urinary and circulatory netrin-1 as biomarker in diabetes and its related complications: a systematic review and meta-analysis.Endocrine · 2024Pooled it
- The effect of intra-articular botulinum toxin A on substance P, prostaglandin EBMC veterinary research · 2017Trial
- Misoprostol in Refractory Neuralgic Pain: From Clinical Neurology to an EP-Receptor Hypothesis of Pharmacodynamic Persistence.International journal of molecular sciences · 2026Review
- Non-Invasive Physical Plasma Regulates COX-2 via EP2/EP4 Expression in Periodontal Ligament Cells Under Inflammatory Conditions.International journal of molecular sciences · 2026Article
- Short-term blockade of E-prostanoid 3 receptor mitigates necroinflammation and ameliorates ischemia/reperfusion- and doxorubicin-induced acute myocardial injury.Basic research in cardiology · 2026Article
- Inhibiting mPGES-2 impedes renal cyst growth in mice with polycystic kidney disease.Acta pharmacologica Sinica · 2026Article
- Unveiling the significance of Netrin-1 and Netrin-4 in metabolic syndrome.Scientific reports · 2026Article
- The dual pathological roles and targeted therapy of PGEFrontiers in pharmacology · 2026Review
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- miR-27a-3p Upregulation and Netrin-1 Deficiency Drive Inflammatory Responses and Nerve Degeneration in Patients With Diabetes.European journal of neurology · 2025Article
- Targeting prostaglandin ENature communications · 2025Article
- Direct Effects of the Janus Kinase Inhibitor Baricitinib on Sensory Neurons.International journal of molecular sciences · 2024Article
- Schwann cell-secreted PGECell · 2024Article
- PGE2 Potentiates Orai1-Mediated Calcium Entry Contributing to Peripheral Sensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons.Scientific reports · 2023Review
- Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors.Science translational medicine · 2022Article
- When Differential Descending Control of Speed Matters: Descending Modulation of A- versus C-Fiber Evoked Spinal Nociception.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Cross-effect of TRPV1 and EP3 receptor on coughs and bronchopulmonary C-neural activities.PloS one · 2021Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception.Journal of neuroinflammation · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pain mediator prostaglandin E2 (PGE2) sensitizes nociceptive pathways through EP2 and EP4 receptors, which are coupled to Gs proteins and increase cAMP. However, PGE2 also activates EP3 receptors, and the major signaling pathway of the EP3 receptor splice variants uses inhibition of cAMP synthesis via Gi proteins. This opposite effect raises the intriguing question of whether the Gi-protein-coupled EP3 receptor may counteract the EP2 and EP4 receptor-mediated pronociceptive effects of PGE2. We found extensive localization of the EP3 receptor in primary sensory neurons and the spinal cord. The selective activation of the EP3 receptor at these sites did not sensitize nociceptive neurons in healthy animals. In contrast, it produced profound analgesia and reduced responses of peripheral and spinal nociceptive neurons to noxious stimuli but only when the joint was inflamed. In isolated dorsal root ganglion neurons, EP3 receptor activation counteracted the sensitizing effect of PGE2, and stimulation of excitatory EP receptors promoted the expression of membrane-associated inhibitory EP3 receptor. We propose, therefore, that the EP3 receptor provides endogenous pain control and that selective activation of EP3 receptors may be a unique approach to reverse inflammatory pain. Importantly, we identified the EP3 receptor in the joint nerves of patients with painful osteoarthritis.
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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.