Foot Care Division, Department of Endocrinology and Metabolism, PGIMER, Chandigarh, 160012, India.
Diabetes and Endocrinology Department, Tameside and Glossop Integrated Care NHS FT, Ashton Under Lyne, Lancs, OL69RW, UK.
Diabetes Metab Syndr. 2021 Jan-Feb;15(1):287-293. doi: 10.1016/j.dsx.2021.01.004. Epub 2021 Jan 11.
Painful diabetic neuropathy significantly affects the quality of life in people with diabetic peripheral neuropathy (DPN). Existing pharmacological agents have limited efficacy and development of tolerance is a limitation.
The present review focuses on novel pharmacological (systemic and topical) and non-pharmacological modalities for the alleviation of pain in people with DPN. We identified English language articles concerning studies with novel agents (animal or human) targeting symptomatic relief of painful diabetic neuropathy.
Though the pathophysiology of pain in DPN is complex, a better understanding of pain pathways (peripheral and central) have helped to identify potential targets for therapeutic success. Studies of pharmacological agents acting on various aspects of pain pathways including μ-opioid receptor agonist- norepinephrine reuptake inhibitor (MONRI), cannabinoid receptor, dual serotonin-nor-adrenergic (SNRI)-and triple dopamine reuptake inhibitor (SNDRI), purinergic receptors and sodium channel v1.7 blockers have undergone trials in humans and shown to improve pain symptoms and quality of life in people with DPN. A few other investigational agents targeting acetylcholine receptor, vanilloid channel, chemokine signaling, micro-RNA or mesenchymal stem cell based therapies (animal studies) have demonstrated promise in alleviation of pain. Topical agents like high-dose lidocaine, capsaicin, clonidine, amitriptyline and ketamine may benefit refractory neuropathic pain.
Novel MONRI, SNRI and cannabinoid receptor agonists have shown some promise for neuropathic pain relief in human trials, but await regulatory approvals. However, most of the novel pharmacological agents (systemic or topical) require appropriately powered placebo-controlled studies for clinical usage in painful diabetic neuropathy.
疼痛性糖尿病周围神经病变显著影响糖尿病周围神经病变（DPN）患者的生活质量。现有药物的疗效有限，且产生耐药性是一个限制因素。
本综述重点介绍了用于缓解 DPN 患者疼痛的新型药理学（全身和局部）和非药理学方法。我们确定了有关针对疼痛性糖尿病周围神经病变症状缓解的新型药物（动物或人类）的英语文章。
尽管 DPN 疼痛的病理生理学很复杂，但对疼痛途径（周围和中枢）的更好理解有助于确定治疗成功的潜在靶点。研究了作用于疼痛途径各个方面的药物，包括μ-阿片受体激动剂-去甲肾上腺素再摄取抑制剂（MONRI）、大麻素受体、双重 5-羟色胺-去甲肾上腺素（SNRI）和三重多巴胺再摄取抑制剂（SNDRI）、嘌呤能受体和钠离子通道 v1.7 阻滞剂，已在人类中进行了试验，并显示出可改善 DPN 患者的疼痛症状和生活质量。一些其他针对乙酰胆碱受体、香草素通道、趋化因子信号、微小 RNA 或间充质干细胞的治疗药物（动物研究）已证明在缓解疼痛方面有一定的希望。局部药物，如高剂量利多卡因、辣椒素、可乐定、阿米替林和氯胺酮，可能对难治性神经病理性疼痛有益。
新型 MONRI、SNRI 和大麻素受体激动剂在人类试验中显示出对神经病理性疼痛缓解有一定的希望，但仍需监管部门批准。然而，大多数新型药理学药物（全身或局部）需要进行适当的、有安慰剂对照的研究，以在疼痛性糖尿病周围神经病变中临床使用。
