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The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors

Costa, Barbara, Comelli, Francesca, Bettoni, Isabella, Colleoni, Mariapia, Giagnoni, Gabriella·2008·Pain

DOI 10.1016/j.pain.2008.06.003

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Abstract

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.

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Authors: Costa, B., Comelli, F., Bettoni, I., Colleoni, M., & Giagnoni, G.
Affiliations: University of Milano-Bicocca (IT)
University of Milan (IT)
Corresponding author: Costa, Barbara
ORCID: Costa, Barbara
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-10-31
Volume: 139
Issue: 3
Pages: 541-550
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/j.pain.2008.06.003
OpenAlex: W2162105352
Cited by: 286
References: 70
Citations by year: 2026: 5 · 2025: 6 · 2024: 11 · 2023: 11 · 2022: 15 · 2021: 20 · 2020: 17 · 2019: 17 · 2018: 20 · 2017: 18 · 2016: 18 · 2015: 19 · 2014: 22 · 2013: 23 · 2012: 19
FWCI: 10.41
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
BOA (University of Milano-Bicocca) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: palmitoylethanolamide, neuropathic pain, chronic constriction injury, thermal hyperalgesia, mechanical allodynia, CB1 receptor, TRPV1 receptor, PPARγ, entourage effect, mast cell degranulation, TNF-α, nerve growth factor, neurotrophic factors, analgesic mechanism
MeSH terms: Amides, Animals, Cytoplasmic Granules, Drug Evaluation, Preclinical, Ethanolamines, Hot Temperature, Hyperalgesia, Ligation, Mast Cells, Nerve Growth Factors, Palmitic Acids, Physical Stimulation, Sciatic Nerve, Sciatica, Spinal Cord, Touch, Tumor Necrosis Factor-alpha, NF-kappa B, Analgesics, Non-Narcotic, Receptor, Cannabinoid, CB1, PPAR alpha, PPAR gamma, TRPV Cation Channels, Mice, Endocannabinoids

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The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors

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