Endocannabinoids control spasticity in a multiple sclerosis model
Endocannabinoids control spasticity in a multiple sclerosis model
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DOI：
10.1096/fj.00-0399fje
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发表时间：
2001-02-01
期刊：
影响因子：
4.8
通讯作者：
Di Marzo, V
中科院分区：
文献类型：
--
作者：
Baker, D;Pryce, G;Di Marzo, V
痉挛状态是多发性硬化症的一个复杂体征，在小鼠慢性复发性实验性自身免疫性脑脊髓炎（CREAE）模型中也会出现。在与神经损伤相关的区域中，检测到内源性大麻素，花生四烯酸乙醇酰胺（AEA）和2-花生四烯酸甘油（2-AG）以及AEA同系物棕榈酰乙醇酰胺（PEA）的水平增加，而在正常和非痉挛CREAE小鼠中发现这些化合物的水平相当。虽然外源性给予内源性大麻素和PEA改善痉挛，但内源性大麻素再摄取和水解的选择性抑制剂-可能通过增强内源性AEA水平，以及可能的2-花生四烯酸甘油-显著改善痉挛，其程度与先前观察到的强效大麻素受体激动剂相当。这些研究为内源性大麻素系统对痉挛的强直控制提供了明确的证据，并为多发性硬化症和其他神经肌肉疾病的治疗开辟了新的视野，这些疾病基于调节内源性大麻素水平和作用的药物，这些药物几乎没有表现出精神活性。
Spasticity is a complicating sign in multiple sclerosis that also develops in a model of chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice. In areas associated with nerve damage, increased levels of the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2‐arachidonoyl glycerol (2‐AG), and of the AEA congener, palmitoylethanolamide (PEA), were detected here, whereas comparable levels of these compounds were found in normal and non‐spastic CREAE mice. While exogenously administered endocannabinoids and PEA ameliorate spasticity, selective inhibitors of endocannabinoid re‐uptake and hydrolysis—probably through the enhancement of endogenous levels of AEA, and, possibly, 2‐arachidonoyl glycerol—significantly ameliorated spasticity to an extent comparable with that observed previously with potent cannabinoid receptor agonists. These studies provide definitive evidence for the tonic control of spasticity by the endocannabinoid system and open new horizons to therapy of multiple sclerosis, and other neuromuscular diseases, based on agents modulating endocannabinoid levels and action, which exhibit little psychotropic activity.