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微粉化棕榈酸乙醇酰胺配方在大鼠术后疼痛中的预防和治疗作用。

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

机构信息

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.

出版信息

Int J Mol Sci. 2020 Oct 18;21(20):7700. doi: 10.3390/ijms21207700.

DOI:10.3390/ijms21207700
PMID:33080989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7589788/
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.

摘要

背景

术后疼痛(PO)是一种常见的急性疼痛形式。PO 治疗不足是一个重要的健康问题,因为它会导致更糟糕的后果,如慢性术后疼痛。因此,有必要获得关于 PO 机制的新知识,以开发比目前更有效的治疗方法,并降低不良反应的风险。出于这个原因,我们评估了微粒化棕榈酰乙醇酰胺(PEA-m)在动物 PO 模型中缓解后爪切开后激活的疼痛和炎症过程的能力。

方法

将动物进行爪部手术切开,并随机分为不同组。PEA-m 在切开前后的不同时间点以 10mg/kg 的剂量口服给药。

结果

我们的研究表明,PEA-m 的预治疗和治疗后可减少切口部位肥大细胞的激活和其致痛介质神经生长因子(NGF)在腰椎脊髓中的表达。此外,在脊髓水平,它还能降低磷酸细胞外信号调节激酶(p-ERK)、离子钙结合衔接分子 1(Iba1)、胶质纤维酸性蛋白(GFAP)和脑源性神经营养因子(BDNF)的激活。PEA-m 还减少了核因子 kappa-轻链增强子的 B 细胞(NF-κB)脊髓途径,在 PO 大鼠模型中表现出保护作用。

结论

研究结果强化了 PEA-m 可能是控制与 PO 相关的疼痛和炎症过程的潜在治疗方法的观点。此外,PEA-m 的术前和术后治疗比手术后单独治疗更有效,这限制了服用化合物的时间和滥用镇痛药。

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