Additive analgesic effect of dexmedetomidine and dezocine administered intrathecally in a mouse pain model.
Additive analgesic effect of dexmedetomidine and dezocine administered intrathecally in a mouse pain model.
复制标题
右美托咪定和地佐辛在小鼠疼痛模型中鞘内给药的附加镇痛作用。
DOI：
10.18632/oncotarget.25304
复制
发表时间：
2018-05-11
期刊：
影响因子：
--
通讯作者：
Yao YX
中科院分区：
文献类型：
--
作者：
Huang YQ;Guo SH;Liu R;Zhu SM;Sun JL;Yao YX
已知右旋美托咪晚可减少阿片样物质需求，并且当右旋美托咪晚和吗啡（完全μ阿片样物质受体激动剂）一起施用时存在协同效应。然而，尚不清楚当右美托咪定与部分μ阿片受体激动剂联合给药时是否会观察到协同或累加效应。本研究旨在通过在小鼠疼痛模型中鞘内共同给予右美托咪定和曲马多辛（一种部分mu受体激动剂）来阐明这种作用。C57小鼠（N = 165）随机分为19组。采用甩尾法测定受试药物的镇痛作用。将小鼠分为生理盐水组和药物组，以研究剂量依赖性镇痛作用。每种药物以固定剂量单独给药，并与第二种药物的三种剂量之一联合给药。地佐辛（0.3125 ~ 1.25 μg）和右美托咪定（0.04 ~ 1 μg）均能剂量依赖性地延长小鼠的缩尾潜伏期。右美托咪定（0.04 ~ 1 μg）可增强曲马多辛的镇痛作用。地佐辛（0.3125 ~ 1.25 μg）可增强右美托咪定的镇痛作用。与单独药物作用相比，注射后15 - 60 min，西洛辛（0.625 μg）和右美托咪定（0.04 μg）的联合作用更强，但仍与两种单独药物作用的总和相似。右美托咪定和曲马多辛同时给药时，对急性伤害性感受产生累加镇痛作用。
It is known that dexmedetomidine can reduce opioid requirements and that there is a synergistic effect when dexmedetomidine and morphine (a full mu opioid receptor agonist) are administered together. However, it was unclear whether a synergistic or additive effect would be observed when dexmedetomidine was co-administered with a partial mu opioid receptor agonist. The present study was designed to elucidate such effects by intrathecally co-administering dexmedetomidine and dezocine, a partial mu receptor agonist, in a mouse pain model. C57 mice (N = 165) were randomly divided into 19 groups. The tail flick test was adopted to measure the antinociceptive effects of the tested agents. The mice were divided into saline and drug groups to investigate the dose-dependent analgesic effects. Each drug was administered at fixed doses alone and in combination with one of three doses of a second drug. Dezocine (0.3125 - 1.25 μg) and dexmedetomidine (0.04 - 1 μg) both enhanced the tail withdrawal latency in dose-dependent fashions. Dexmedetomidine (0.04 - 1 μg) enhanced the analgesic effect of dezocine. Dezocine (0.3125 - 1.25 μg) enhanced the analgesic effect of dexmedetomidine. Compared with the individual drug effects, the combined effects of dezocine (0.625 μg) and dexmedetomidine (0.04 μg) were more potent 15 - 60 min after injection, but they remained similar to the sum of the effects of the two individual drugs. Dexmedetomidine and dezocine produce an additive analgesic effect on acute nociception when administered simultaneously.