Metformin: A Prospective Alternative for the Treatment of Chronic Pain.
Metformin: A Prospective Alternative for the Treatment of Chronic Pain.
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DOI：
10.3389/fphar.2020.558474
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发表时间：
2020
影响因子：
5.6
通讯作者：
Granados-Soto V
中科院分区：
文献类型：
--
作者：
Baeza-Flores GDC;Guzmán-Priego CG;Parra-Flores LI;Murbartián J;Torres-López JE;Granados-Soto V
二甲双胍（双胍）是一种广泛用于治疗2型糖尿病的药物。这种药作为一种非常有效的降糖药已经使用了60年。对二甲双胍作用机制的探索已经产生了大量的研究，以解释其对糖异生、蛋白质代谢、脂肪酸氧化、氧化应激、葡萄糖摄取、自噬和疼痛等方面的影响。直到20世纪90年代末和本世纪初，它的一些机制才被揭示出来。二甲双胍通过激活一种名为amp活化蛋白激酶（AMPK）的主开关激酶来诱导其对糖尿病的有益作用。两种上游激酶负责AMPK的生理激活：肝激酶B1和钙/钙调素依赖性蛋白激酶激酶2。AMPK一旦被激活，就会抑制雷帕霉素复合物1 （mTORC1）的机制靶点，从而避免p70核糖体蛋白S6激酶1和磷脂酰肌醇3-激酶/蛋白激酶B信号通路的磷酸化，并减少帽依赖性翻译起始。由于二甲双胍是2型糖尿病的一种疾病改善药物，它可以降低mTORC1信号传导从而诱导其对神经元可塑性的影响，因此有人提出这些机制也可以解释该药物在几种慢性疼痛模型中的抗伤害感受作用。这些研究强调了该药对慢性疼痛的疗效，如神经病变、胰岛素抵抗、糖尿病性神经病变和纤维肌痛型疼痛。越来越多的证据表明，慢性疼痛可能会导致啮齿动物和人类的焦虑、抑郁和认知障碍。有趣的是，二甲双胍能够逆转啮齿动物病理性疼痛的一些后果。本综述的目的是分析二甲双胍对慢性疼痛及其三种合并症（焦虑、抑郁和认知障碍）的影响的现有证据。
Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).
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影响因子：
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作者：
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通讯作者：
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影响因子：
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发表时间：
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作者：
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