Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats
Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats
复制标题
DOI：
10.1016/j.ejphar.2006.07.027
复制
发表时间：
2006-09-28
影响因子：
5
通讯作者：
Cruz, Silvia L.
中科院分区：
文献类型：
--
作者：
Hernandez-Delgadillo, Gloria P.;Cruz, Silvia L.
低剂量阿片类药物与非甾体抗炎药联合给药可产生相加或超相加镇痛作用，同时减少不必要的副作用。我们最近报道，共同管理的吗啡与安乃近（安乃近）产生镇痛增效在天真和吗啡耐受大鼠。本工作的目的是确定阿片类药物对大鼠甩尾试验中观察到的吗啡和安乃近静脉注射之间的急性增强作用的作用。为此，我们做了两个实验。第一组在吗啡（3.1mg/kg）、安乃近（600 mg/kg）或吗啡与安乃近联合用药前10 min给予纳洛酮。对照组动物接受生理盐水代替纳洛酮。在第二个实验中，在每次单独镇痛治疗达到最大峰值效应后2分钟给予纳洛酮（或生理盐水）。当纳洛酮在镇痛药之前静脉给药时，它完全阻断吗啡作用，部分阻止吗啡/安乃近抗伤害性感受，并延迟安乃近诱导的伤害性感受。在3.1 mg/kg剂量下，纳洛酮产生的伤害性感受增加。当在镇痛药后给予纳洛酮时，其剂量依赖性地阻断吗啡单独和与安乃近组合的作用，但在每种情况下具有不同的效力。与安乃近相比，纳洛酮使镇痛作用达峰时间延迟。两者合计，这些结果支持的概念，即内源性阿片样物质参与观察到的镇痛增效与吗啡加安乃近的组合。(c)2006 Elsevier B. V.保留所有权利。
The combined administration of low doses of opiates with non-steroidal anti-inflammatory drugs can produce additive or supra-additive analgesic effects while reducing unwanted side effects. We have recently reported that co-administration of morphine with dipyrone (metamizol) produces analgesic potentiation both in naive and in morphine-tolerant rats. The purpose of this work was to determine the role of opioids on the acute potentiation observed between morphine and dipyrone i.v. in the rat tail flick test. To do this, two experiments were done. In the first one, naloxone was administered 10 min before morphine (3.1 mg/kg), dipyrone (600 mg/kg) or their combination at the same doses. Control animals received saline instead of naloxone. In the second experiment, naloxone (or saline) was given 2 min after reaching the maximal peak effect with each individual analgesic treatment. When naloxone was i.v. administered prior to analgesics, it completely blocked morphine effects, partially prevented morphine/dipyrone antinociception and delayed dipyrone-induced nociception. At 3.1 mg/kg, naloxone produced an increased nociception. When naloxone was given after analgesics, it dose-dependently blocked the effects of morphine alone and in combination with dipyrone but with different potency in each case. As to dipyrone, naloxone delayed the time to antinociceptive peak effect. Taken together, these results support the notion that endogenous opioids are involved in the analgesic potentiation observed with the combination of morphine plus dipyrone. (c) 2006 Elsevier B.V. All rights reserved.