ArticlePloS one2013
Full inhibition of spinal FAAH leads to TRPV1-mediated analgesic effects in neuropathic rats and possible lipoxygenase-mediated remodeling of anandamide metabolism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Association between the FAAH C385A variant (rs324420) and obesity-related traits: a systematic review.International journal of obesity (2005) · 2024Pooled it
- Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data.The journal of pain · 2015Pooled it
- A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Phase I Study of Analgesic/Antihyperalgesic Properties of ASP8477, a Fatty Acid Amide Hydrolase Inhibitor, in Healthy Female Subjects.Pain medicine (Malden, Mass.) · 2018Trial
- Role of Concentration in Opposing Effects of Anandamide on Nociceptive Synapses versus Non-nociceptive Synapses.eNeuro · 2026Article
- Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms.International journal of molecular sciences · 2025Review
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.Neuropharmacology · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of blood flow restriction training for knee pain: a mini review.Frontiers in physiology · 2025Review
- Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level.Physiological research · 2024Review
- Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.Cells · 2024Article
- The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization.Frontiers in molecular neuroscience · 2024Review
- URB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Activity of FAAH-Inhibitor JZP327A in an Experimental Rat Model of Migraine.International journal of molecular sciences · 2023Article
- Fatty acid amide hydrolase and 9-lipoxygenase modulate cotton seedling growth by ethanolamide oxylipin levels.Plant physiology · 2023Article
- Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain.International journal of molecular sciences · 2022Review
- Endocannabinoid system and its modulation of brain, gut, joint and skin inflammation.Molecular biology reports · 2021Review
- Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain.International journal of molecular sciences · 2021Article
- Anti-nociceptive effect of Arbutus andrachne L. methanolic leaf extract mediated by CB1, TRPV1 and PPARs in mouse pain models.Inflammopharmacology · 2020Article
- Thymus algeriensis and Thymus fontanesii exert neuroprotective effect against chronic constriction injury-induced neuropathic pain in rats.Scientific reports · 2020Article
- Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI) of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX), and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats.
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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.