Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.
Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.
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DOI：
10.1093/brain/awad283
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发表时间：
2024-01-04
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影响因子：
--
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不宁腿综合征（RLS）对阿片类、多巴胺能和铁剂治疗有反应。对不宁腿综合征患者进行的受体阻滞剂研究表明，阿片类药物的治疗效果对阿片受体具有特异性，并通过多巴胺能系统间接介导。一项不宁腿综合征的尸检研究显示，不宁腿综合征患者丘脑中内源性阿片类物质、β -内啡肽以及可能还有蛋氨酸 - 脑啡肽减少。一种阿片受体完全敲除（μ、δ和κ）以及一种μ - 阿片受体敲除的不宁腿综合征小鼠模型显示出与不宁腿综合征类似的昼夜节律性运动变化，并且尽管两种模型都显示出感觉变化，但μ - 阿片受体敲除小鼠显示出的昼夜节律性感觉变化与特发性不宁腿综合征中所见最为接近。两种模型都显示出纹状体多巴胺、贫血和血清铁降低的变化。然而，只有在阿片受体完全敲除的小鼠中我们才看到不宁腿综合征中通常出现的血清铁蛋白降低。当给野生型小鼠施用μ - 阿片受体阻滞剂时，血清铁也会降低。此外，μ - 阿片受体敲除小鼠还显示出纹状体锌增加，这与不宁腿综合征中的类似变化相符。促肾上腺皮质激素和α - 黑素细胞刺激素与β - 内啡肽一样都来源于阿黑皮素原。然而，当将它们脑室内注射到大鼠体内时，会引起类似不宁腿综合征的症状和周期性肢体运动。这些结果共同表明，内源性阿片类物质缺乏是不宁腿综合征的发病原因，并且黑素皮质素系统的改变也可能是不宁腿综合征的病因。
沃尔特斯等人综述了来自人体尸检研究和动物模型的证据，这些证据表明内啡肽和脑啡肽等内源性阿片系统的缺乏有助于不宁腿综合征的发病。
Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well. Walters et al. review evidence from human autopsy studies and animal models suggesting that a deficiency in the endogenous opioid system of endorphins and enkephalins contributes to the pathogenesis of restless legs syndrome.
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影响因子：
4.8
作者：
Dowsett, Joseph;Didriksen, Maria;Ullum, Henrik
通讯作者：
Ullum, Henrik
影响因子：
3.4
作者：
Walters, Arthur S.;Zee, Phyllis C.
通讯作者：
Zee, Phyllis C.
DOI：
10.1093/ecam/nep132
发表时间：
2011
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Cheng CH;Yi PL;Lin JG;Chang FC
通讯作者：
Chang FC
影响因子：
4.8
作者：
Earley, Christopher J.;Hyland, Keith;Allen, Richard P.
通讯作者：
Allen, Richard P.
影响因子：
4.8
作者：
Cho, Yong Won;Kang, Min-Sung;Motamedi, Gholam K.
通讯作者：
Motamedi, Gholam K.