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Cited by 288Pain Mechanisms and TreatmentsCannabis and Cannabinoid ResearchIon Channels and Receptors

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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Crossref · 10.1016/j.pain.2008.06.003

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  • Daily administration of PEA in a mouse model of CCI for a week produces a long-lasting reduction of nociceptive behavior in nerve-injured animals after cessation of PEA treatment.

    “Interestingly, daily administration of PEA in a mouse model of CCI for a week produces a longlasting reduction of nociceptive behavior in nerve-injured animals after cessation of PEA treatment (Costa et al, 2008).”

    From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Costa et al, 2008

  • The fatty acid amide PEA, a substrate of FAAH and an endogenous PPARα ligand, produces antinociceptive effects in a rat pSNL model and in a mouse CCI model.

    “In addition, the fatty acid amide PEA, a substrate of FAAH and an endogenous PPARα ligand, produces antinociceptive effects in a rat pSNL model and in a mouse CCI model (Di Cesare Mannelli et al, 2013;Costa et al, 2008).”

    From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Costa et al, 2008

  • PEA administered chronically attenuates the development of thermal hyperalgesia and mechanical allodynia in the CCI model through CB1, PPARγ, and TRPV1-mediated mechanisms.

    “The fatty acid PEA, administered chronically, attenuated the development of thermal hyperalgesia and mechanical allodynia in the CCI model through CB1, PPARγ and TRPV1-mediated mechanisms.60”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [60]

  • Chronic administration of PEA normalizes levels of NGF, GDNF, and NT-3 that were increased by CCI.

    “Chronic administration of PEA also normalized levels of three neutrophic factors (NGF, GDNF, and NT-3) that were increased by CCI.60”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [60]

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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 › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Pharmacology › 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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