Document Detail


Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain.
MedLine Citation:
PMID:  17449181     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oleoylethanolamide (OEA) is a natural fatty acid amide that mainly modulates feeding and energy homeostasis by binding to peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [Rodríguez de Fonseca F, Navarro M, Gómez R, Escuredo L, Navas F, Fu J, et al. An anorexic lipid mediator regulated by feeding. Nature 2001;414:209-12; Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez de Fonseca F, et al. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003;425:90-3]. Additionally, it has been proposed that OEA could act via other receptors, including the vanilloid receptor (TRPV1) [Wang X, Miyares RL, Ahern GP. Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol 2005;564:541-7.] or the GPR119 receptor [Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006;3:167-175], suggesting that OEA might subserve other physiological roles, including pain perception. We have evaluated the effect of OEA in two types of nociceptive responses evoked by visceral and inflammatory pain in rodents. Our results suggest that OEA has analgesic properties reducing the nociceptive responses produced by administration of acetic acid and formalin in two experimental animal models. Additional research was performed to investigate the mechanisms underlying this analgesic effect. To this end, we evaluated the actions of OEA in mice null for the PPAR-alpha receptor gene and compared its actions with those of PPAR-alpha receptor wild-type animal. We also compared the effect of MK-801 in order to evaluate the role of NMDA receptor in this analgesia. Our data showed that OEA reduced visceral and inflammatory responses through a PPAR-alpha-activation independent mechanism. Co-administration of subanalgesic doses of MK-801 and OEA produced an analgesic effect, suggesting the participation of glutamatergic transmission in the antinociceptive effect of OEA. This study represents a novel approach to the examination of the effectiveness of OEA in nociceptive responses and provides a framework for understanding its biological functions and endogenous targets in visceral and inflammatory pain.
Authors:
Margarita Suardíaz; Guillermo Estivill-Torrús; Carlos Goicoechea; Ainhoa Bilbao; Fernando Rodríguez de Fonseca
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-20
Journal Detail:
Title:  Pain     Volume:  133     ISSN:  1872-6623     ISO Abbreviation:  Pain     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-27     Completed Date:  2008-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7508686     Medline TA:  Pain     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  99-110     Citation Subset:  IM    
Affiliation:
Fundación IMABIS, Unidad de Investigación, Hospital Universitario Carlos Haya, Málaga 29010, Spain.
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MeSH Terms
Descriptor/Qualifier:
Analgesics / therapeutic use*
Animals
Anticholesteremic Agents / pharmacology
Behavior, Animal / drug effects
Disease Models, Animal
Dizocilpine Maleate / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Antagonists / pharmacology
Exploratory Behavior / drug effects
Inflammation / complications
Male
Mice
Mice, Knockout
Morphine / therapeutic use
Oleic Acids / therapeutic use*
PPAR gamma / deficiency
Pain / classification,  drug therapy*,  etiology,  genetics
Pain Measurement / drug effects,  methods
Pyrimidines / pharmacology
Chemical
Reg. No./Substance:
0/Analgesics; 0/Anticholesteremic Agents; 0/Excitatory Amino Acid Antagonists; 0/Oleic Acids; 0/PPAR gamma; 0/Pyrimidines; 0/oleoylethanolamide; 50892-23-4/pirinixic acid; 57-27-2/Morphine; 77086-22-7/Dizocilpine Maleate

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