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The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, Italy
Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Via Consolare Valeria, 98125 Messina, Italy
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
Institute of Anaesthesiology and Reanimation, Catholic University of the Sacred Heart, 00168 Rome, Italy
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104 , USA
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7700;
Received: 24 September 2020 / Revised: 16 October 2020 / Accepted: 16 October 2020 / Published: 18 October 2020
(This article belongs to the Special Issue Palmitoylethanolamide)
Background: Postoperative pain (PO) is a common form of acute pain. Inadequate PO treatment is an important health problem, as it leads to worse outcomes, such as chronic post-surgical pain. Therefore, it is necessary to acquire new knowledge on PO mechanisms to develop therapeutic options with greater efficacy than those available today and to lower the risk of adverse effects. For this reason, we evaluated the ability of micronized palmitoylethanolamide (PEA-m) to resolve the pain and inflammatory processes activated after incision of the hind paw in an animal model of PO. Methods: The animals were subjected to surgical paw incision and randomized into different groups. PEA-m was administered orally at 10 mg/kg at different time points before or after incision. Results: Our research demonstrated that the pre- and post-treatment with PEA-m reduced the activation of mast cells at the incision site and the expression of its algogenic mediator nerve growth factor (NGF) in the lumbar spinal cord. Furthermore, again at the spinal level, it was able to decrease the activation of phospho-extracellular signal-regulated kinases (p-ERK), ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the expression of brain-derived neurotrophic factor (BDNF). PEA-m also reduced the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) spinal pathway, showing a protective effect in a rat model of PO. Conclusion: The results obtained reinforce the idea that PEA-m may be a potential treatment for the control of pain and inflammatory processes associated with PO. In addition, pre- and post-treatment with PEA-m is more effective than treatment alone after the surgery and this limits the time of taking the compound and the abuse of analgesics. View Full-Text
Keywords: palmitoylethanolamide; inflammation; pain; biochemical and therapeutic advances palmitoylethanolamide; inflammation; pain; biochemical and therapeutic advances
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Siracusa, R.; Fusco, R.; Cordaro, M.; Peritore, A.F.; D’Amico, R.; Gugliandolo, E.; Crupi, R.; Genovese, T.; Evangelista, M.; Di Paola, R.; Cuzzocrea, S.; Impellizzeri, D. The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats. Int. J. Mol. Sci. 2020, 21, 7700.

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