ArticleThe Journal of pharmacology and experimental therapeutics2008
Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and met-enkephalin in the rat ventrolateral periaqueductal gray.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.Equine veterinary journal · 2017Trial
- Dimethoxybenzohomoadamantane-based soluble epoxide hydrolase inhibitors:Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Inhibition of Soluble Epoxide Hydrolase Prevents Docetaxel-Induced Painful Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- Regulatory lipid vicinal diols counteract the biological activity of epoxy fatty acids and can act as biomarkers and mechanisms for disease progression.Pharmacology & therapeutics · 2023Review
- Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers.Clinics (Sao Paulo, Brazil) · 2023Article
- Relationship between fatty acid intake and chronic neck/shoulder/upper limb pain without elevated CRP in a Japanese population: a cross-sectional analysis of the Shika study.Journal of nutritional science · 2022Article
- Acid-sensing ion channel 1a in the central nucleus of the amygdala regulates anxiety-like behaviors in a mouse model of acute pain.Frontiers in molecular neuroscience · 2022Article
- Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis.Frontiers in veterinary science · 2021Article
- Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke.Frontiers in cellular neuroscience · 2021Article
- Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies.The Journal of nutritional biochemistry · 2020Review
- Review
- Oxidized Lipids in Persistent Pain States.Frontiers in pharmacology · 2019Review
- Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism.Frontiers in molecular neuroscience · 2019Review
- Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia.Scientific reports · 2018Article
- Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus.Neural plasticity · 2017Article
- Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation.Archives of toxicology · 2016Article
- Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray.Reproductive sciences (Thousand Oaks, Calif.) · 2016Article
- Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE₂ induced pain model.Toxicology and applied pharmacology · 2015Article
- Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs.Advances in nutrition (Bethesda, Md.) · 2015Review
- Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 genes catalyze formation of epoxyeicosatrienoic acids (EETs) from arachidonic acid. The effects of 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET microinjected into the ventrolateral periaqueductal gray (vlPAG) on the thermally produced tail-flick response were studied in male Sprague-Dawley rats. 14,15-EET microinjected into vlPAG (3-156 pmol) dose-dependently inhibited the tail-flick response (ED50 = 32.5 pmol). In contrast, 5,6-EET, 8,9-EET, and 11,12-EET at a dose of 156 pmol were not active when injected into the vlPAG. 14,15-EET failed to displace the radiobinding of [3H][D-Ala2,NHPe4, Gly-ol5]enkephalin (mu-opioid receptor ligand) or [3H]naltrindole (delta-opioid receptor ligand) in crude membrane fractions of rat brain. Tail-flick inhibition produced by 14,15-EET from vlPAG was blocked by intra-vlPAG pretreatment with antiserum against beta-endorphin or Met-enkephalin or the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or the delta-opioid receptor antagonist naltrindole but not with dynorphin A[1-17] antiserum or the kappa-opioid receptor antagonist nor-binaltorphimine. In addition, tail-flick inhibition produced by 14,15-EET treatment was blocked by intrathecal pretreatment with Met-enkephalin antiserum, naltrindole, or CTOP but not with beta-endorphin antiserum. It is concluded that 1) 14,15-EET itself does not have any affinity for mu- or delta-opioid receptors and 2) 14,15-EET activates beta-endorphin and Met-enkephalin, which subsequently act on mu- and delta-opioid receptors to produce antinociception.
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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.