ArticleProceedings of the National Academy of Sciences of the United States of America2009
Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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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.
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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
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).BMJ (Clinical research ed.) · 2016Pooled it
- Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.BMJ (Clinical research ed.) · 2021Trial
- Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain.BMC musculoskeletal disorders · 2016Trial
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- Effect of Preoperative Pain on Inferior Alveolar Nerve Block.Anesthesia progress · 2015Trial
- A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.Prostaglandins, leukotrienes, and essential fatty acids · 2014Trial
- Trial
- Trial
- Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans.Prostaglandins, leukotrienes, and essential fatty acidsTrial
- Sepsis-associated acute lung injury: do inflammatory lipid mediators flood the lungs by activating pulmonary TRP channels?Intensive care medicine experimental · 2026Review
- Triamcinolone acetonide nanoparticles ameliorate interstitial cystitis and anxiety/depression by targeting the bladder-metabolic-brain axis.Materials today. Bio · 2026Article
- Integrative Pharmacokinetic and Metabolomic Analyses Reveal the Underlying Mechanisms of Metabolic Regulation and Support the Safe Use of Oxolinic Acid inAntioxidants (Basel, Switzerland) · 2026Article
- Article
- 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
- Jasmine sambac L. essential oil attenuates inflammation and pain via TRPV1.Inflammopharmacology · 2025Article
- System-wide targeted analysis of oxylipins and lipoproteins in chronic peripheral neuropathic pain-an explorative study.Pain reports · 2025Article
- Transcriptomic profiling identifies ferroptosis and NF-κB signaling involved in α-dimorphecolic acid regulation of microglial inflammation.Journal of translational medicine · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- The association between dietary fat quality and quantity and hospitalization duration in COVID-19 in Iranian patients: a cross-sectional study.Frontiers in nutrition · 2025Article
- TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Transient receptor potential vanilloid 1 (TRPV1) plays a major role in hyperalgesia and allodynia and is expressed both in the peripheral and central nervous systems (CNS). However, few studies have evaluated mechanisms by which CNS TRPV1 mediates hyperalgesia and allodynia after injury. We hypothesized that activation of spinal cord systems releases endogenous TRPV1 agonists that evoke the development of mechanical allodynia by this receptor. Using in vitro superfusion, the depolarization of spinal cord triggered the release of oxidized linoleic acid metabolites, such as 9-hydroxyoctadecadienoic acid (9-HODE) that potently activated spinal TRPV1, leading to the development of mechanical allodynia. Subsequent calcium imaging and electrophysiology studies demonstrated that synthetic oxidized linoleic acid metabolites, including 9-HODE, 13-HODE, and 9 and 13-oxoODE, comprise a family of endogenous TRPV1 agonists. In vivo studies demonstrated that intrathecal application of these oxidized linoleic acid metabolites rapidly evokes mechanical allodynia. Finally, intrathecal neutralization of 9- and 13-HODE by antibodies blocks CFA-evoked mechanical allodynia. These data collectively reveal a mechanism by which an endogenous family of lipids activates TRPV1 in the spinal cord, leading to the development of inflammatory hyperalgesia. These findings may integrate many pain disorders and provide an approach for developing analgesic drugs.
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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.