Gong Ya-Hong, Yu Xue-Rong, Liu Hui-Li, Yang Nan, Zuo Ping-Ping, Huang Yu-Guang
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Acta Anaesthesiol Taiwan. 2011 Mar;49(1):16-20. doi: 10.1016/j.aat.2011.01.003. Epub 2011 Mar 17.
The purpose of this study was to establish the streptozotocin (STZ)-induced diabetic model with rats and investigate the antinociceptive effect of combination of Tramadol (TR) and Acetaminophen (NAPA) on the animal model for the first time.
Diabetic model was induced by a single injection of STZ (60 mg/kg, intraperitoneal). Nociceptive thresholds were measured by means of electronic von Frey test, hot-plate test, and tail-flick test. On the 28th day of diabetes induction, diabetic rats with significant hyperalgesia were randomly divided into three groups: TR, NAPA, and TR-NAPA combination group. Each group was randomly divided into four subgroups. Three geometric series of drugs were given to each group respectively. Antinociceptive effects of the drugs were assessed at 15, 30, 60, 120, and 180 minutes after drug administration. 50% Maximum antinociceptive effect of each drug was determined by probit analysis, whereas interaction between TR and NAPA was evaluated by isobolographic analysis.
Hyperalgesia, along with hyperglycemia, developed 4 days after STZ injection and persisted at all tested time points until 28 days. TR, NAPA, and TR-NAPA combination administration all produced dose-dependent antinociceptive effects. Isobolographic analysis showed a significant deviation of TR/NAPA 50% maximum antinociceptive effect (in tail-flick test, but not in von Frey test) from the additive line.
Combination of the two drugs produces an additive antinociceptive effect in tail-flick test, whereas probable additive antinociceptive effect in von Frey test in painful diabetic neuropathy rats.
本研究旨在建立链脲佐菌素（STZ）诱导的大鼠糖尿病模型，并首次研究曲马多（TR）与对乙酰氨基酚（NAPA）联合用药对该动物模型的镇痛作用。
通过单次腹腔注射STZ（60mg/kg）诱导糖尿病模型。采用电子von Frey试验、热板试验和甩尾试验测量痛阈。在糖尿病诱导的第28天，将具有明显痛觉过敏的糖尿病大鼠随机分为三组：TR组、NAPA组和TR-NAPA联合组。每组再随机分为四个亚组。分别给每组给予三个几何级数的药物。在给药后15、30、60、120和180分钟评估药物的镇痛效果。通过概率分析确定每种药物的50%最大镇痛效果，而通过等效应线图分析评估TR和NAPA之间的相互作用。
痛觉过敏与高血糖一起在STZ注射后4天出现，并在所有测试时间点持续至28天。TR、NAPA和TR-NAPA联合给药均产生剂量依赖性镇痛作用。等效应线图分析显示，TR/NAPA 50%最大镇痛效果（在甩尾试验中，但在von Frey试验中未出现）与相加线有显著偏差。
在甩尾试验中，两种药物联合使用产生相加性镇痛作用，而在糖尿病性疼痛性神经病变大鼠的von Frey试验中可能产生相加性镇痛作用。
