1. 2017;20;E401-E409Dezocine Antagonizes Morphine Analgesia upon Simultaneous Administration in Rodent Models of Acute Nociception
   Animal Study
   Sheng-Mei Zhu, MD, Chen-Ling Guo, BS, Maxwell R. Shen, MBBS, Shao-Hui Guo, MS, Ling-Er Huang, BS, Ya-Qin Huang, MS, Na-na Li, MS, and Yong-Xing Yao, MD.

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