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Isobolographic analysis of the cutaneous antinociceptive interaction between bupivacaine co-injected with serotonin in rats

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Abstract

Background

The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception.

Methods

The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug-drug interactions were evaluated by isobologram.

Results

Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37–0.50] μmol) > serotonin (1.27 [1.15–1.40] μmol) (p < 0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception.

Conclusions

The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine + serotonin than bupivacaine alone.

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Author notes

  1. These authors contributed equally

Authors and Affiliations

  1. Department of Anesthesiology, Chi Mei Medical Center, Yong Kang, Tainan, Taiwan

    Jann-Inn Tzeng

  2. Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan

    Chong-Chi Chiu

  3. Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Chong-Chi Chiu

  4. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan

    Jhi-Joung Wang & Yu-Wen Chen

  5. Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Health Care, China Medical University, Taichung, Taiwan

    Yu-Wen Chen

  6. Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ching-Hsia Hung

  7. Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ching-Hsia Hung

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  1. Jann-Inn Tzeng
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  2. Chong-Chi Chiu
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Correspondence to Yu-Wen Chen.

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Tzeng, JI., Chiu, CC., Wang, JJ. et al. Isobolographic analysis of the cutaneous antinociceptive interaction between bupivacaine co-injected with serotonin in rats. Pharmacol. Rep 69, 846–850 (2017). https://doi.org/10.1016/j.pharep.2017.03.017

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  • DOI: https://doi.org/10.1016/j.pharep.2017.03.017

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