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

@article{Costa2008TheEF,
  title={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 PPAR$\gamma$ receptors and neurotrophic factors},
  author={Barbara Costa and Francesca Comelli and Isabella Bettoni and Mariapia Colleoni and Gabriella Giagnoni},
  journal={PAIN},
  year={2008},
  volume={139},
  pages={541-550}
}

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References

SHOWING 1-10 OF 78 REFERENCES
The palmitoylethanolamide family: a new class of anti-inflammatory agents?
TLDR
In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.
Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo‐oxygenase systems
TLDR
It is shown, for the first time, that palmitoylethanolamide has a curative effect in a model of acute inflammation, inhibiting the carrageenan‐induced oedema in a dose‐ and time‐dependent manner.
Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat
TLDR
The antiinflammatory effect of nabilone is shown and that of palmitoylethanolamide is confirmed indicating that these actions are mediated by an uncharacterized CB2‐like cannabinoid receptor.
A Novel Neuroimmune Mechanism in Cannabinoid-mediated Attenuation of Nerve Growth Factor–induced Hyperalgesia
TLDR
Cannabinoids show a neuronal CB1 receptor–mediated antihyperalgesic action and a separate inhibition of a proinflammatory neuroimmune process, which suggests a therapeutic site of analgesic action separable from central side effects.
Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems
TLDR
PEA enhances the VR1‐mediated effects of AEA and capsaicin on calcium influx into cells, and could underlie the enhancement by PEA, described here for the first time, of the antiproliferative effects of VR1 receptor agonists.
Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats
...
...