Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
Physiophathology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
Pharmacol Rep. 2018 Jun;70(3):503-508. doi: 10.1016/j.pharep.2017.11.012. Epub 2017 Nov 22.
Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated.
A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models.
PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia.
The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain.
紫杉醇（PTX）给药和部分坐骨神经结扎（PSNL）可在小鼠中诱导神经性疼痛和随后的超敏反应。由于缺乏有效治疗方法，其药物治疗一直是临床挑战。在两种小鼠神经性疼痛模型（PTX 和 PSNL）中，评估了瑞舒伐他汀的镇痛作用以及促炎生物标志物白细胞介素（IL）-1β、TBARS 和谷胱甘肽的参与情况。
通过冷板、热板和 Von Frey 测定法获得瑞舒伐他汀 ip 的剂量-反应曲线。在 PTX 和 PSNL 小鼠模型中，在第 7 天和第 14 天测量脊髓中 IL-1β、谷胱甘肽和脂质过氧化水平的变化。
PTX 或 PSNL 能够在 7 天和 14 天诱导小鼠周围神经病变和超敏反应。瑞舒伐他汀在热板、冷板和 Von Frey 测定法中诱导了剂量依赖性镇痛作用。PTX 或 PSNL 预处理引起的 IL-1β 或 TBARS 水平升高被瑞舒伐他汀降低。PTX 或 PSNL 引起的脊髓谷胱甘肽减少，以 GSH/GSSG 比值表示，在用瑞舒伐他汀预处理的动物中显著增加。他汀类药物的抗炎特性可能通过降低促炎生物标志物和激活神经胶质来解释其对神经性疼痛的有益作用。
本研究的结果表明瑞舒伐他汀在治疗神经性疼痛方面具有潜在的用途。
