ArticleMolecular pain2012
The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain.
Article in Molecular pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain.International journal of molecular sciences · 2025Review
- Truncated TrkB: The predominant TrkB isoform in nociceptors.The journal of pain · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice.Scientific reports · 2023Article
- Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice.bioRxiv : the preprint server for biology · 2023Article
- Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients.Metabolites · 2023Article
- The expression pattern, subcellular localization and function of three sterol 14α-demethylases inFrontiers in genetics · 2023Article
- Review
- Molecular Pathways Linking Oxylipins to Nociception in Rats.The journal of pain · 2021Article
- Epoxy Fatty Acids Are Promising Targets for Treatment of Pain, Cardiovascular Disease and Other Indications Characterized by Mitochondrial Dysfunction, Endoplasmic Stress and Inflammation.Advances in experimental medicine and biology · 2020Review
- Linoleic acid-derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron-glia co-cultures in a sex-dependent manner.Journal of neurochemistry · 2020Article
- Systematically Characterize the Anti-Alzheimer's Disease Mechanism of Lignans fromMolecules (Basel, Switzerland) · 2019Article
- Oxidized Lipids in Persistent Pain States.Frontiers in pharmacology · 2019Review
- Roles of TRPV1 and TRPA1 in Spontaneous Pain from Inflamed Masseter Muscle.Neuroscience · 2018Article
- TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.Acta physiologica (Oxford, England) · 2018Article
- Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1.The journal of pain · 2017Article
- Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice.The American journal of pathology · 2017Article
- A proteomic analysis of acute leukemia cells treated with 9-hydroxyoctadecadienoic acid.Lipids in health and disease · 2016Article
- Role of Oxidized Lipids and TRP Channels in Orofacial Pain and Inflammation.Journal of dental research · 2016Review
- TRP channels and traffic-related environmental pollution-induced pulmonary disease.Seminars in immunopathology · 2016Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundOxidized linoleic acid metabolites (OLAMs) are a class of endogenous agonists to the transient receptor potential V1 (TRPV1) receptor. Although TRPV1 mediates inflammatory heat hyperalgesia, it is not known if the OLAMs contribute to the peripheral activation of this receptor during tissue inflammation. In the present study, we evaluated whether the OLAM system is activated during inflammation and whether cytochrome P450 enzymes mediate OLAM contributions to heat hyperalgesia using the complete Freund's adjuvant (CFA) model of inflammation.
resultsOur results demonstrate that the intraplantar (ipl) injection of anti-OLAM antibodies significantly reversed CFA-induced heat hyperalgesia. Moreover, application of lipid extracts from inflamed rat skin to cultured sensory neurons triggered a significant release of iCGRP that is blocked by co-treatment with I-RTX, a TRPV1 antagonist. To determine the role of CYP enzymes in mediating OLAM effects, we used a broad spectrum CYP inhibitor, ketoconazole. Pretreatment with ketoconazole inhibited the release of TRPV1 agonists in lipid extracts from inflamed skin and significantly reversed CFA-induced heat hyperalgesia by a peripheral mechanism of action. Moreover, the ipl injection of linoleic acid to rats 24 hr after CFA evoked spontaneous nocifensive behaviors that were significantly reduced by capsazepine, by knockout of the TRPV1 gene, or by pretreatment with either anti-OLAM antibodies or ketoconazole.
conclusionsTaken together, our data suggests that OLAMs contribute to inflammatory nociception in the periphery and that cytochrome P450 enzymes play a crucial role in mediating OLAM contributions to inflammatory heat hyperalgesia.
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