Abstract
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.
Highlights
Pain is considered a negative experience associated with tissue damage
A large number of surgical procedures take place every year throughout the world [4]. Such surgical interventions lead to a series of consequences including high mortality and morbidity rates that reach 10 and 16%, respectively; high costs of treatment of chronic pain resulting from acute pain; and, economic losses to society [5,6]
A number of studies have been conducted to evaluate the role of the endocannabinoid system in nociceptive processing and its potential target for inducing analgesia, especially because cannabinoid receptors and ligands are found at almost all levels of pain from peripheral to central sites [14]
Summary
Pain is considered a negative experience associated with tissue damage. The distinction between acute and chronic pain remains the most common and generally determines the choice of drug therapy [1]. The oral administration of PEA is capable of reducing the paw edema induced by carrageenan, dextran, and formalin These studies suggest that PEA can modulate the activation of mast cells and suppress the inflammatory responses that are activated following the degranulation of mast cells [19]. The pharmacological characteristics of PEA and the results demonstrated in various experimental models have stimulated our research on the evaluation of PEA in its micronized form (PEA-m) in an animal model of acute postoperative pain in order to demonstrate the ability of this compound to resolve the pain and inflammatory processes activated after a surgical incision. WWee ddiidd nnoott ddeetteecctt aa ssiiggnniifificcaanntt rreedduuccttiioonniinn aanniimmaallss ooff tthhee PPOO ++ PPEEAA--mm ppoosstt--ttrreeaattmmeenntt ggrroouupp ((FFiigguurree 33DD aanndd tthhee rreellaattiivvee ggrraapphhininFFigiguurere3E3)E. I)n. sItnesatdea, dPE, APE-mA-pmrep+repo+stp-toresta-ttmreeantmt seignntifisicgannitfliycarnedtluycreeddtuhceeldevtehles olfevtheilssporfottehiins (pFriogtuerien 3(FCigaunrdet3hCe raenldatitvhee grerlaapthiviengFriagpuhrein3EF)ig. ure 3E)
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