ArticleEuropean journal of pain (London, England)2017
Epoxy fatty acids mediate analgesia in murine diabetic neuropathy.
Article in European journal of pain (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Randomized, double-blind, phase 1a single-ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers.Clinical and translational science · 2024Trial
- Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.Journal of veterinary pharmacology and therapeutics · 2018Trial
- Allosteric ensembles elucidate mechanisms of inhibition in the human soluble epoxide hydrolase.Communications biology · 2026Article
- Dimethoxybenzohomoadamantane-based soluble epoxide hydrolase inhibitors:Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Mitochondrial Gene Regulation and Pain Susceptibility: A Multi-Omics Causal Inference Study.International journal of molecular sciences · 2025Article
- How Robust Is the Ligand Binding Transition State?Journal of the American Chemical Society · 2023Article
- Dihydroxy-Metabolites of Dihomo-γ-linolenic Acid Drive Ferroptosis-Mediated Neurodegeneration.ACS central science · 2023Article
- The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling.Journal of translational medicine · 2023Article
- Dihydroxy-Metabolites of Dihomo-gamma-linolenic Acid Drive Ferroptosis-Mediated Neurodegeneration.bioRxiv : the preprint server for biology · 2023Article
- Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers.Clinics (Sao Paulo, Brazil) · 2023Article
- The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.Prostaglandins & other lipid mediators · 2022Article
- Soluble Epoxide Hydrolase and Diabetes Complications.International journal of molecular sciences · 2022Review
- Article
- 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
- Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals.Diabetes & metabolism journal · 2021Review
- Lack of rewarding effects of a soluble epoxide hydrolase inhibitor TPPU in mice: Comparison with morphine.Neuropsychopharmacology reports · 2020Article
- Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies.The Journal of nutritional biochemistry · 2020Review
- Soluble epoxide hydrolase inhibitor mediated analgesia lacks tolerance in rat models.Brain research · 2020Article
- Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids.Journal of lipid research · 2018Article
- Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases.Pharmacology & therapeutics · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega-3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics.
methodsWe tested diabetic neuropathic wild-type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu-opioid receptor antagonist.
resultsThe EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids.
conclusionsThe EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions. SIGNIFICANCE: EDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects.
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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.