ArticlePloS one2010
R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 81 citations in OpenAlex.
- Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Trial
- The Activation of Aldehyde Dehydrogenase 2 (ALDH2) by Alda-1 and Flurbiprofen as a Common Mechanism to Reduce Alcohol Intake in Rats.International journal of molecular sciences · 2026Article
- The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex.International journal of molecular sciences · 2025Article
- Article
- Assessment of NSAIDs as potential inhibitors of the fatty acid amide hydrolase I (FAAH-1) using three different primary fatty acid amide substrates in vitro.BMC pharmacology & toxicology · 2022Article
- Increased Fat Taste Preference in Progranulin-Deficient Mice.Nutrients · 2021Article
- The Comparison of Plasma and Cerebrospinal Fluid R(-)- and S(+)-Flurbiprofen Concentration After Intravenous Injection of Flurbiprofen Axetil in Human Subjects.Frontiers in pharmacology · 2021Article
- NSAIDs Naproxen, Ibuprofen, Salicylate, and Aspirin Inhibit TRPM7 Channels by Cytosolic Acidification.Frontiers in physiology · 2021Article
- Low brain endocannabinoids associated with persistent non-goal directed nighttime hyperactivity after traumatic brain injury in mice.Scientific reports · 2020Article
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Flurbiprofen loaded ethosomes - transdermal delivery of anti-inflammatory effect in rat model.Lipids in health and disease · 2019Article
- Sensitization of nociceptors by prostaglandin EBlood · 2019Article
- Pharmacological Treatment of Chemotherapy-Induced Neuropathic Pain: PPARγ Agonists as a Promising Tool.Frontiers in neuroscience · 2019Review
- Lipopolysaccharide from Rhodobacter sphaeroides (TLR4 antagonist) attenuates hypersensitivity and modulates nociceptive factors.Pharmaceutical biology · 2018Article
- New approaches and challenges to targeting the endocannabinoid system.Nature reviews. Drug discovery · 2018Review
- Therapeutic Effect of the Substrate-Selective COX-2 Inhibitor IMMA in the Animal Model of Chronic Constriction Injury.Frontiers in pharmacology · 2018Article
- Blockade of P2X4 Receptors Inhibits Neuropathic Pain-Related Behavior by Preventing MMP-9 Activation and, Consequently, Pronociceptive Interleukin Release in a Rat Model.Frontiers in pharmacology · 2017Article
- R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4.International journal of molecular sciences · 2016Article
- Endocannabinoids as Guardians of Metastasis.International journal of molecular sciences · 2016Review
- Pro-inflammatory obesity in aged cannabinoid-2 receptor-deficient mice.International journal of obesity (2005) · 2016Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundR-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL
findingsWe show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists.
conclusionOur results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.
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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.