Dezocine Antagonizes Morphine Analgesia upon Simultaneous Administration in Rodent Models of Acute Nociception.
Dezocine Antagonizes Morphine Analgesia upon Simultaneous Administration in Rodent Models of Acute Nociception.
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DOI：
10.36076/ppj.2017.e409
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发表时间：
2017-03
期刊：
影响因子：
3.7
通讯作者：
Na-Na Li-Na;Ya-Qin Huang;Ling-Er Huang;Shao-hui Guo;Maxwell R. Shen;Chen-Ling Guo;Sheng-Mei Zhu;Yong-Xing Yao
中科院分区：
文献类型：
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作者：
Na-Na Li-Na;Ya-Qin Huang;Ling-Er Huang;Shao-hui Guo;Maxwell R. Shen;Chen-Ling Guo;Sheng-Mei Zhu;Yong-Xing Yao
地佐辛是一种强效镇痛药，其成瘾性低于吗啡，但这两种药物在体内如何相互作用尚不清楚。在这里，我们给药单药或与吗啡组合不同的急性伤害性感受范例，以探讨共同给药后的2种药物的相互作用。目的研究不同急性伤害性感受模式下马槟榔碱与吗啡的相互作用。研究设计实验室动物研究。单位：浙江大学医学院。方法：健康小鼠分别用生理盐水、马诺辛（0.625 - 2.5 μg）或马诺辛与吗啡（2.5 μg）联合给药。在给药前和给药后30分钟分析缩尾潜伏期（TWL）。用盐水、吗啡（3 mg/kg）、曲马多辛（3 mg/kg）或两种药物的组合处理大鼠。然后动物不受伤，进行足底切开，或进行甲醛诱导的急性炎症。然后根据对von Frey刺激的机械阈值（MT）和对热刺激的缩爪潜伏期（PWL）分析伤害感受。根据动物咬腿和抬高腿的持续时间计算甲醛诱导的疼痛评分。在足底切口后还测量了细胞外信号调节激酶（pERK）的磷酸化，作为伤害感受的分子指标。结果地佐辛呈剂量依赖性地增强小鼠TWL，抑制吗啡镇痛。在未受伤的大鼠中单独使用吗啡或长春新碱增加MT，但同时使用两种药物并没有进一步增加MT。在切开后30分钟，相对于生理盐水，单独使用一种药物和两种药物一起使用增加了MT和PWL。单独使用一种药物，而不是两种药物一起使用，增加MT和PWL在120分钟后切口。地佐辛减少了甲氨蝶呤诱导的伤害性感受，但同时给予两种药物并没有进一步减少疼痛行为。局限性结果来自动物研究;需要临床研究来阐明它们的相互作用。结论地佐辛同时给药可拮抗吗啡对急性伤害性感受的镇痛作用。
BACKGROUND Dezocine is a powerful analgesic that can be less addictive than morphine, yet how the two drugs interact in vivo is poorly understood. Here we administered dezocine alone or in combination with morphine to different acute nociception paradigms to explore the interactions of the 2 drugs upon co-administration. OBJECTIVE To evaluate how dezocine interacts with morphine in different acute nociception paradigms. STUDY DESIGN Laboratory animal study. SETTING Zhejiang University School of Medicine, Hangzhou, China. METHODS Healthy mice were treated with saline, dezocine (0.625 - 2.5 µg), or a combination of dezocine with morphine (2.5 µg). Tail withdrawal latency (TWL) was analyzed prior to and 30 minutes after drug administration. Rats were treated with saline, morphine (3 mg/kg), dezocine (3 mg/kg), or a combination of both drugs. The animals were then left uninjured, subjected to plantar incision, or underwent formaldehyde-induced acute inflammation. Nociception was then analyzed in terms of mechanical threshold (MT) to von Frey stimulation and paw withdrawal latency (PWL) to thermal stimulation. Formaldehyde-induced pain score was calculated based on the duration of biting and elevating of the animal's legs. Phosphorylation of extracellular signal-regulated kinase (pERK) was also measured after plantar incision as a molecular index of nociception. RESULTS Dezocine enhanced TWL but inhibited morphine analgesia in a dose-dependent fashion in mice. Usage of morphine or dezocine alone in uninjured rats increased MT, but co-administering both drugs did not further increase MT. Usage of one drug alone, and both drugs together increased MT and PWL relative to saline at 30 minutes after incision. Usage of one drug alone, but not both drugs together, increased MT and PWL at 120 minutes after incision. Dezocine reduced formaldehyde-induced nociception but co-administering both drugs did not further reduce pain behavior. LIMITATIONS The results were obtained from animal study; clinical investigations will be needed to clarify their interaction. CONCLUSION Dezocine antagonizes morphine analgesia on acute nociception upon simultaneous administration.Key words: Dezocine, morphine, acute nociception, analgesia.