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加巴喷丁与米诺环素在小鼠糖尿病性神经病变中的抗伤害感受相互作用。

Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.

作者信息

Miranda H F, Sierralta F, Jorquera V, Poblete P, Prieto J C, Noriega V

机构信息

Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile.

Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile.

出版信息

Inflammopharmacology. 2017 Feb;25(1):91-97. doi: 10.1007/s10787-017-0308-5. Epub 2017 Feb 28.

Abstract

OBJECTIVE

Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ).

METHODS

The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice.

RESULTS

STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test.

CONCLUSION

The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.

摘要

目的

糖尿病神经病变(DN)是糖尿病最常见的并发症,疼痛是糖尿病神经病变的主要症状之一,然而,目前可用的药物往往无效且伴有不良事件。本研究的目的是通过链脲佐菌素(STZ)在小鼠DN实验模型中评估加巴喷丁和米诺环素之间的镇痛相互作用。

方法

在雄性CF1小鼠注射STZ或赋形剂后3天和7天,通过扭体试验和热板试验评估加巴喷丁与米诺环素的相互作用。

结果

STZ(150mg/kg,腹腔注射)在第7天(397.46±±29.65mg/dL)比第3天(341.12±±35.50mg/dL)使血浆葡萄糖水平显著升高,并且通过痛觉测定法测得出现了神经性疼痛。加巴喷丁在STZ预处理的小鼠的扭体试验和热板试验中均产生了类似的镇痛活性。然而,在同一类型的小鼠中,米诺环素在扭体试验中的效力比在热板试验中更强。加巴喷丁与米诺环素的组合在两种试验中均产生了协同相互作用。

结论

加巴喷丁与米诺环素按1:1比例组合符合多模式镇痛的所有标准,这一发现表明该组合提供了一种可用于人类神经性疼痛管理的治疗选择。

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