Document Detail


The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors.
MedLine Citation:
PMID:  18602217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Palmitoylethanolamide (PEA) is an endogenous lipid that is thought to be involved in endogenous protective mechanisms activated as a result of stimulation of inflammatory response. In spite of the well demonstrated anti-inflammatory properties of PEA, its involvement in controlling pain pathways still remains poorly characterized. On this basis, we tested the efficacy of PEA in vivo against a peculiar persistent pain, such as neuropathic one. PEA was administered i.p. to mice with chronic constriction injury of sciatic nerve (CCI) once a day for one week starting the day after the lesion. This therapeutic regimen evoked a relief of both thermal hyperalgesia and mechanical allodynia in neuropathic mice. Various selective receptor antagonists were used in order to clarify the relative contribution of cannabinoid, vanilloid and peroxisome proliferator-activated receptor to PEA-induced effects. The results indicated that CB(1), PPARgamma and TRPV1 receptors mediated the antinociception induced by PEA, suggesting that the most likely mechanism might be the so-called "entourage effect" due to the PEA-induced inhibition of the enzyme catalyzing the endocannabinoid anandamide (AEA) degradation that leads to an enhancement of its tissue levels thus increasing its analgesic action. In addition, the hypothesis that PEA might act through the modulation of local mast cells degranulation is sustained by our findings showing that PEA significantly reduced the production of many mediators such as TNFalpha and neurotrophic factors, like NGF. The findings presented here, in addition to prove the beneficial effects of PEA in chronic pain, identify new potential targets for analgesic medicine.
Authors:
Barbara Costa; Francesca Comelli; Isabella Bettoni; Mariapia Colleoni; Gabriella Giagnoni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-03
Journal Detail:
Title:  Pain     Volume:  139     ISSN:  1872-6623     ISO Abbreviation:  Pain     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2009-08-07     Completed Date:  2009-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7508686     Medline TA:  Pain     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  541-50     Citation Subset:  IM    
Affiliation:
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Italy. barbara.costa@unimib.it
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MeSH Terms
Descriptor/Qualifier:
Analgesics, Non-Narcotic / pharmacology,  therapeutic use*
Animals
Cytoplasmic Granules / secretion
Drug Evaluation, Preclinical
Hot Temperature / adverse effects
Hyperalgesia / drug therapy*,  etiology,  physiopathology
Ligation
Mast Cells / drug effects*,  secretion
Mice
NF-kappa B / physiology
Nerve Growth Factors / secretion*
PPAR alpha / antagonists & inhibitors
PPAR gamma / antagonists & inhibitors,  physiology*
Palmitic Acids / pharmacology,  therapeutic use*
Physical Stimulation / adverse effects
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  physiology*
Sciatic Nerve / injuries
Sciatica / drug therapy*,  physiopathology
Spinal Cord / chemistry
TRPV Cation Channels / antagonists & inhibitors,  physiology*
Touch
Tumor Necrosis Factor-alpha / analysis
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/NF-kappa B; 0/Nerve Growth Factors; 0/PPAR alpha; 0/PPAR gamma; 0/Palmitic Acids; 0/Receptor, Cannabinoid, CB1; 0/TRPV Cation Channels; 0/TRPV1 protein, mouse; 0/Tumor Necrosis Factor-alpha; 544-31-0/palmidrol

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