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
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
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DOI：
10.1016/j.pain.2008.06.003
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发表时间：
2008-10-31
期刊：
影响因子：
7.4
通讯作者：
Giagnoni, Gabriella
中科院分区：
文献类型：
--
作者：
Costa, Barbara;Comelli, Francesca;Giagnoni, Gabriella
棕榈酰乙醇胺（PEA）是一种内源性脂质，被认为参与刺激炎症反应激活的内源性保护机制。尽管PEA具有良好的抗炎特性，但其参与控制疼痛通路的特征仍然很差。在此基础上，我们测试了PEA在体内对一种特殊的持续性疼痛的疗效，例如Lis神经性疼痛。从损伤后第二天开始，将PEA腹膜内给予患有慢性坐骨神经压迫性损伤（CCI）的小鼠，每天一次，持续一周。这种治疗方案引起了缓解热痛觉过敏和机械异常性疼痛的神经病小鼠。为了阐明大麻素、香草素和过氧化物酶体增殖物激活受体对PEA诱导效应的相对贡献，使用了各种选择性受体拮抗剂。结果表明，CB1、PPARgamma和TRPV1受体介导了PEA的镇痛作用，其机制可能是PEA抑制内源性大麻素花生四烯酸（AEA）的降解，从而提高其组织水平，从而增强其镇痛作用，从而产生所谓的“随行效应”。此外，PEA可能通过调节局部肥大细胞脱颗粒而起作用的假设被我们的发现所支持，该发现表明PEA显著减少了许多介质如TNF α和神经营养因子如NGF的产生。这里提出的研究结果，除了证明PEA在慢性疼痛中的有益作用外，还确定了镇痛药物的新的潜在靶点。2008年国际疼痛研究协会。Elsevier B.V.出版，保留所有权利。
Palmitoylethanolamide (PEA) is an endogenous lipid that is thought to be involved in endogenOUS protective mechanisms activated as a result of stimulation of inflammatory response. In spite of the well demonstrated anti-inflammatory properties of PEA, its involvement in controlling pain pathways still remains poorly characterized. On this basis, we tested the efficacy of PEA in vivo against a Peculiar persistent pain, such Lis neuropathic one. PEA was administered i.p. to mice with chronic constriction injury of sciatic nerve (CCI) once a day for one week starting the day after the lesion. This therapeutic regimen evoked a relief of both thermal hyperalgesia and mechanical allodynia in neuropathic mice. Various selective receptor antagonists were used in order to clarify the relative contribution of cannabinoid, vanilloid and peroxisome proliferator-activated receptor to PEA-induced effects. The results indicated that CB1, PPAR gamma and TRPV1 receptors mediated the antinociception induced by PEA, suggesting that the most likely mechanism might be the so-called "entourage effect" due to the PEA-induced inhibition of the enzyme catalyzing the endocannabinoid anandamide (AEA) degradation that leads to an enhancement of its tissue levels thus increasing its analgesic action. In addition, the hypothesis that PEA might act through the modulation of local mast cells degranulation is sustained by our findings showing that PEA significantly reduced the production of many mediators such as TNF alpha, and neurotrophic factors, like NGF. The findings presented here, in addition to prove the beneficial effects of PEA in chronic pain, identify new potential targets for analgesic medicine. 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.