Huang Ya-Qin, Guo Shao-Hui, Liu Renyu, Zhu Sheng-Mei, Sun Jian-Liang, Yao Yong-Xing
Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.
Department of Anesthesia, Hangzhou Hospital Affiliated With Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, P. R. China.
Oncotarget. 2018 May 11;9(36):24391-24397. doi: 10.18632/oncotarget.25304.
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.
已知右美托咪定可减少阿片类药物的用量，且右美托咪定与吗啡（一种完全μ阿片受体激动剂）联合使用时存在协同效应。然而，当右美托咪定与部分μ阿片受体激动剂联合使用时，是否会观察到协同或相加效应尚不清楚。本研究旨在通过在小鼠疼痛模型中鞘内联合给予右美托咪定和地佐辛（一种部分μ受体激动剂）来阐明此类效应。
将165只C57小鼠随机分为19组。采用甩尾试验测量受试药物的镇痛效果。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。每种药物单独以固定剂量给药，并与三种剂量的另一种药物之一联合给药。
地佐辛（0.3125 - 1.25μg）和右美托咪定（0.04 - 1μg）均以剂量依赖性方式延长甩尾潜伏期。右美托咪定（0.04 - 1μg）增强了地佐辛的镇痛效果。地佐辛（0.3125 - 1.25μg）增强了右美托咪定的镇痛效果。与单独药物作用相比，地佐辛（0.625μg）和右美托咪定（0.04μg）联合作用在注射后15 - 60分钟时更强，但仍与两种单独药物作用之和相似。
右美托咪定和地佐辛同时给药时对急性伤害性感受产生相加镇痛作用。
