Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors

Holt, Sandra; Comelli, Francesca; Costa, Barbara; Fowler, Christopher J

doi:10.1038/sj.bjp.0706348

Cited by 177Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsInflammatory mediators and NSAID effects

Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors

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Holt, Sandra, Comelli, Francesca, Costa, Barbara, Fowler, Christopher J·2005·British Journal of Pharmacology

DOI 10.1038/sj.bjp.0706348PMC PMC1576291

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Abstract

The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced hind paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice. Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg−1) 30 min prior to carrageenan administration, dose‐dependently reduced oedema formation. At the 4 h time point, the ED 50 for URB597 was ∼0.3 mg kg−1. Indomethacin (5 mg kg−1 i.p.) completely prevented the oedema response to carrageenan. The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg−1 i.p. of the CB 2 receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator‐activated receptor γ antagonist bisphenol A diglycidyl ether (30 mg kg−1 i.p.) or the TRPV1 antagonist capsazepine (10 mg kg−1 i.p.), when oedema was assessed 4 h after carrageenan administration. The CB 1 receptor antagonists AM251 (3 mg kg−1 i.p.) and rimonabant (0.5 mg kg−1 i.p.) gave inconsistent effects upon the antioedema effect of URB597. FAAH measurements were conducted ex vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in the paws and spinal cords of the inflamed vehicle‐treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg−1) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528‐sensitive anti‐inflammatory effects in the carrageenan model of acute inflammation. British Journal of Pharmacology (2005) 146, 467–476. doi:10.1038/sj.bjp.0706348

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FAAH inhibitors attenuate carrageenan-induced edema, an effect that is mediated through the CB2 receptor.
“FAAH inhibitors also attenuate carrageenaninduced edema, an effect that is mediated through the CB 2 receptor (Holt et al, 2005;Lichtman et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Holt et al, 2005

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Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets
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Anatomical Distribution of Receptors, Ligands and Enzymes in the Brain and in the Spinal Cord: Circuitries and Neurochemistry
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The Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review
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Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw inflammation in the mouse: Comparison with indomethacin and possible involvement of cannabinoid receptors.
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Authors: Holt, S., Comelli, F., Costa, B., & Fowler, C. J.
Affiliations: Umeå University (SE)
University of Milano-Bicocca (IT)
Corresponding author: Holt, Sandra
ORCID: Costa, Barbara
Fowler, Christopher J
Venue: British Journal of Pharmacology
Publisher: Wiley
Published: 2005-10
Volume: 146
Issue: 3
Pages: 467-476
ISSN: 0007-1188 (ISSN-L)
1476-5381
DOI: 10.1038/sj.bjp.0706348
PMC: PMC1576291
OpenAlex: W2027176103
Cited by: 168
References: 61
Citations by year: 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 10
FWCI: 13.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1216 d)
Locations: British Journal of Pharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
BOA (University of Milano-Bicocca) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords: fatty acid amide hydrolase inhibitors, URB597, indomethacin, carrageenan-induced paw edema, hindpaw inflammation, cannabinoid receptors, CB2 receptor, CB1 receptor, anti-inflammatory activity, analgesia, endocannabinoids, edema, SR144528, rimonabant, AM251
MeSH terms: Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Anti-Inflammatory Agents, Non-Steroidal, Benzamides, Camphanes, Brain, Carbamates, Carrageenan, Disease Models, Animal, Enzyme Inhibitors, Hindlimb, Indomethacin, Inflammation, Male, Mice, Inbred C57BL, Pentobarbital, Phenylmethylsulfonyl Fluoride, Pyrazoles, Spinal Cord, Mice, Cannabinoid Receptor Antagonists

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Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors

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