Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy
Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy
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DOI：
10.1038/s41393-018-0168-x
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发表时间：
2018-11-01
期刊：
影响因子：
2.2
通讯作者：
Dehpour, Ahmad Reza
中科院分区：
文献类型：
--
作者：
Afshari, Khashayar;Dehdashtian, Amir;Dehpour, Ahmad Reza
目的二甲双胍是一种安全的糖尿病血糖控制药物。已经显示二甲双胍改善脊髓损伤（SCI）后的运动恢复。神经性疼痛也是SCI的一个令人不安的组成部分。二甲双胍具有神经保护和抗炎作用，可减轻神经病理性疼痛和受损神经的痛觉过敏。因此，我们评估了二甲双胍对SCI神经炎症及其感觉和运动并发症的治疗作用。方法建立大鼠脊髓损伤动物模型，48只雄性大鼠行T9椎板切除术。将动物分为假手术组和五个治疗组。处理包括生理盐水作为溶剂对照组，米诺环素90 mg/kg和二甲双胍10、50和100 mg/kg剂量。运动量表，神经性疼痛和体重变化的行为测试进行了评估和比较，通过28天的时间。结果50 mg/kg的Metalloy可明显改善大鼠的运动能力（p < 0.001），降低对机械和热异常性疼痛的敏感性（p < 0.01）。这些结果与米诺环素对脊髓损伤的作用一致（p > 0.05）。二甲双胍可导致体重减轻，二甲双胍和米诺环素均可显著降低脊髓组织病理学检查中的神经炎症，降低TNF-α和白细胞介素-113水平（p < 0.001）。结论二甲双胍可作为脊髓损伤的替代治疗药物，因为它可能减轻脊髓损伤的神经炎症、感觉和运动并发症。
Study design This is an animal study.Objectives Metformin is a safe drug for controlling blood sugar in diabetes. It has been shown that metformin improves locomotor recovery after spinal cord injury (SCI). Neuropathic pain is also a disturbing component of SCI. It is indicated that metformin has neuroprotective and anti-inflammatory effects, which attenuate neuropathic pain and hyperalgesia in injured nerves. Thus, we evaluated metformin's therapeutic effects on SCI neuroinflammation and its sensory and locomotor complications. Meanwhile, results were compared to minocycline, an anti-neuroinflammation therapy in SCI.Setting Experimental Medicine Research Center, Tehran University of Medical Sciences, IranMethods In an animal model of SCI, 48 male rats were subjected to T9 vertebra laminectomy. Animals were divided into a SHAM-operated group and five treatment groups. The treatments included normal saline as a vehicle control group, minocycline 90 mg/kg and metformin at the doses of 10, 50 and 100 mg/kg. Locomotor scaling, behavioral tests for neuropathic pain and weight changes were evaluated and compared through a 28-days period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes.Results Metformin 50 mg/kg improved the locomotors ability (p < 0.001) and decreased sensitivity to mechanical and thermal allodynia (p < 0.01). These results were compatible with minocycline effect on SCI (p > 0.05). While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-alpha and interleukin-113 (p < 0.001).Conclusions Metformin could be considered as an alternative therapeutic agent for SCI, as it potentially attenuates neuroinflammation, sensory and locomotor complications of cord injury.