Stefania Nobili , Laura Micheli , Elena Lucarini, Alessandra Toti, Carla Ghelardini, Lorenzo Di Cesare Mannelli
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引用次数: 0
摘要
据目前的流行病学数据估计,每五个人中就有一人患有慢性疼痛,并严重影响与健康相关的生活质量。药物治疗以一线和二线镇痛药物为主,包括 COX-2 选择性和非选择性非甾体抗炎药、扑热息痛、抗抑郁药、抗癫痫药和阿片类药物,这些药物都有很大的副作用。N-棕榈酰乙醇胺(PEA)是人体自身的脂肪酸乙醇酰胺,属于自体局部损伤拮抗剂酰胺家族。数十年来,PEA 的抗炎和止痛特性已得到认可,并促使人们对其在内源性疼痛控制机制中的作用进行描述。新的 PEA 是一种大粒径脂质分子,溶解度和生物利用度都很低。减小粒径是增加表面积的有效方法,从而相应地提高溶解率和生物利用率。与普通 PEA 相比,PEA 的微米级制剂(如超微粒化和共(超)微粒化)显示出更高的口服疗效。尤其是超微粒化的五乙醇胺已被证明能有效穿过肠壁,更重要的是能穿过血脑屏障和血脊髓屏障。本综述总结了超微粒化 PEA 现有的药代动力学/药效学数据,并重点介绍了其对疼痛控制的贡献,尤其是作为 "附加 "营养干预的作用。数据显示,超微粒子化 PEA 能够限制阿片类药物的副作用,包括耐受性的产生。
Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain
Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects.
N-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention.
Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA.
This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as ‘add-on’ nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.
期刊介绍:
Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.