Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms?
Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms?
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DOI：
10.1097/j.pain.0000000000001922
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发表时间：
2020-09
期刊：
影响因子：
7.4
通讯作者：
Calcutt NA
中科院分区：
文献类型：
--
作者：
Calcutt NA
神经病变是长期糖尿病的常见并发症，通过产生疼痛、感觉丧失和截肢来损害生活质量。胰岛素缺乏型（1型）和胰岛素抵抗型（2型）糖尿病患者均存在神经病变，同时1型糖尿病患者通过改善血糖控制来减缓神经病变的进展，这使得大多数临床前和临床研究都将重点放在高血糖作为初始致病病变上。糖尿病动物模型的研究已经确定了多种可能的糖毒性神经系统机制，包括葡萄糖对蛋白质的翻译后修饰以及醛糖还原酶、糖酵解和其他分解代谢途径增加的葡萄糖代谢。然而，越来越明显的是，不一定是高血糖下游的因素也可以促进神经病变和神经性疼痛的发生、进展和严重程度。例如，外周神经中含有胰岛素受体，它能传递胰岛素的神经营养和神经支持特性，独立于全身葡萄糖调节，而在代谢综合征患者中检测到神经病变和神经性疼痛，以及在2型糖尿病患者队列中改善血糖控制以防止神经病变的失败，使得人们关注血脂异常的致病作用。本文综述了目前对糖尿病神经病变潜在初始病变的理解，以及在糖尿病细胞和动物模型中确定的多种下游机制，这些机制可能有助于糖尿病神经病变和神经性疼痛的发病机制。
Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in both insulin-deficient (type 1) and insulin resistant (type 2) diabetes along with the slowing of progression of neuropathy by improved glycemic control in type 1 diabetes has caused the majority of preclinical and clinical investigations to focus on hyperglycemia as the initiating pathogenic lesion. Studies in animal models of diabetes have identified multiple plausible mechanisms of glucotoxicity to the nervous system including post-translational modification of proteins by glucose and increased glucose metabolism by aldose reductase, glycolysis and other catabolic pathways. However, it is becoming increasingly apparent that factors not necessarily downstream of hyperglycemia can also contribute to the incidence, progression and severity of neuropathy and neuropathic pain. For example, peripheral nerve contains insulin receptors that transduce the neurotrophic and neurosupportive properties of insulin, independent of systemic glucose regulation, while the detection of neuropathy and neuropathic pain in patients with metabolic syndrome and failure of improved glycemic control to protect against neuropathy in cohorts of type 2 diabetic patients has placed a focus on the pathogenic role of dyslipidemia. This review provides an overview of current understanding of potential initiating lesions for diabetic neuropathy and the multiple downstream mechanisms identified in cell and animal models of diabetes that may contribute to the pathogenesis of diabetic neuropathy and neuropathic pain.
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影响因子：
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