Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

Theodoros Papathanasiou; Rasmus Vestergaard Juul; Anne-Marie Heegaard; Mads Kreilgaard; Trine Meldgaard Lund

doi:10.1016/j.ejps.2015.11.015

Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

Theodoros Papathanasiou, Rasmus Vestergaard Juul, Anne-Marie Heegaard, Mads Kreilgaard, Trine Meldgaard Lund

20 Citationer (Scopus)

Abstract

Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58 % for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose-dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients.

Originalsprog	Dansk
Tidsskrift	European Journal of Pharmaceutical Sciences
Vol/bind	82
Sider (fra-til)	97–105
Antal sider	9
ISSN	0928-0987
DOI	https://doi.org/10.1016/j.ejps.2015.11.015
Status	Udgivet - 20 jan. 2016

Adgang til dokumentet

10.1016/j.ejps.2015.11.015

http://www.sciencedirect.com/science/article/pii/S0928098715300683

Citationsformater

Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain. / Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie et al.

I: European Journal of Pharmaceutical Sciences, Bind 82, 20.01.2016, s. 97–105.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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abstract = "Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58 % for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose-dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients.",

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