Document Detail

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: a role for endogenous fatty-acid ethanolamides?
MedLine Citation:
PMID:  17027744     Owner:  NLM     Status:  MEDLINE    
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of anandamide, an endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs could be due to inhibition of cyclooxygenase (COX) and also to an increase in endocannabinoid concentrations. In a previous study we have demonstrated that the local analgesic interaction between anandamide and ibuprofen (a non-specific COX inhibitor) was synergistic for the acute and inflammatory phases of the formalin test. To test this hypothesis further, we repeated similar experiments with rofecoxib (a selective COX-2 inhibitor) and also measured the local concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide and palmitoylethanolamide. We established the ED(50) for anandamide (34.52 pmol+/-17.26) and rofecoxib (381.72 pmol+/-190.86) and showed that the analgesic effect of the combination was synergistic. We also found that paw tissue levels of anandamide, oleoylethanolamide and palmitoylethanolamide were significantly higher when anandamide was combined with NSAIDs and that this effect was greater with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was antinociceptive in a test of acute and inflammatory pain and the combination of anandamide with rofecoxib was synergistic. Finally, locally injected anandamide with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid ethanolamides. The exact comprehension of the mechanisms involved needs further investigation.
Josée Guindon; Jesse LoVerme; André De Léan; Daniele Piomelli; Pierre Beaulieu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-09-08
Journal Detail:
Title:  European journal of pharmacology     Volume:  550     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-23     Completed Date:  2006-12-15     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  68-77     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine, Université de Montréal - C.P. 6128, Succ. Centre-ville, Montréal, Québec, Canada H2W 1T8.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Arachidonic Acids / pharmacology*
Capsaicin / analogs & derivatives,  pharmacology
Chromatography, High Pressure Liquid
Cyclooxygenase 2 Inhibitors / pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Edema / chemically induced,  drug therapy
Formaldehyde / diagnostic use
Ibuprofen / pharmacology
Lactones / pharmacology
Mass Spectrometry
Nitrobenzenes / pharmacology
Pain Measurement / drug effects
Peripheral Nervous System / drug effects*
Polyunsaturated Alkamides / pharmacology*
Rats, Wistar
Sulfonamides / pharmacology
Sulfones / pharmacology
TRPV Cation Channels / drug effects
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Arachidonic Acids; 0/Cyclooxygenase 2 Inhibitors; 0/Lactones; 0/Nitrobenzenes; 0/Polyunsaturated Alkamides; 0/Sulfonamides; 0/Sulfones; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 0/capsazepine; 0/rofecoxib; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 15687-27-1/Ibuprofen; 404-86-4/Capsaicin; 50-00-0/Formaldehyde; 94421-68-8/anandamide

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