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, 9 (36), 24391-24397

Additive Analgesic Effect of Dexmedetomidine and Dezocine Administered Intrathecally in a Mouse Pain Model

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Additive Analgesic Effect of Dexmedetomidine and Dezocine Administered Intrathecally in a Mouse Pain Model

Ya-Qin Huang et al. Oncotarget.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Dexmedetomidine and dezocine produce an additive analgesic effect on acute nociception when administered simultaneously.

Keywords: acute nociception; analgesia; dexmedetomidine; dezocine.

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Intrathecal dezocine or dexmedetomidine produced dose-dependent antinociception in the tail flick test
Within the 0.3125 - 1.25 μg dose range, 15 min after intrathecal injection, dezocine increased the tail withdrawal latency in a dose-dependent fashion (A). Within the 0.04 - 1 μg dose range, dexmedetomidine increased the tail withdrawal latency in a dose-dependent manner (B). *P < 0.05, **P < 0.01 vs the NS group. Error bars represent the SEM. NS = Normal saline. MPE = Maximum possible effect.
Figure 2
Figure 2. Dose-dependent analgesic effects of dezocine were potentiated by dexmedetomidine and vice versa
At 15 min after intrathecal injection, dexmedetomidine increased the effect of dezocine in a dose-dependent fashion within a dose range of 0.04 - 1 μg (A). At 15 min after intrathecal injection, dezocine increased the effect of dexmedetomidine in a dose-dependent fashion within a dose range of 0.3125 - 1.25 μg (B). *P < 0.05, **P < 0.01 vs the NS group. Error bars represent SEM. NS = Normal saline. MPE = Maximum possible effect.
Figure 3
Figure 3. Additive effect of dezocine combined with dexmedetomidine in a tail flick assay
At 30 minutes after injection, the combined effect of dezocine (0.625 μg) and dexmedetomidine (0.04 μg) was more potent than the effect of dezocine or dexmedetomidine alone. However, this effect remained similar to the sum of the two individual effects. *P < 0.05 vs dezocine, #P < 0.05, ##P < 0.01 vs dexmedetomidine, n = 9. Error bars represent the SEM. NS = Normal saline. MPE = Maximum possible effect.

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