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Synergistic Analgesic Effect of Morphine and Tramadol in Non-Sensitized and Morphine-Sensitized Mice: An Isobolographic Study Publisher Pubmed



Khakpai F1 ; Nedaei F2 ; Shahini F3 ; Zarrindast MR3, 4, 5
Authors
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Authors Affiliations
  1. 1. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Pharmacology and Toxicology, Islamic Azad University, Pharmaceutical Science Branch (IAUPS), Tehran, Iran
  3. 3. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Neuroendocrinology, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Acta Neurobiologiae Experimentalis Published:2021


Abstract

Morphine and tramadol are the opioid analgesic drugs acting via activation of μ-opioid receptors. It is important to understand which mechanism (synergistic or additive anti-nociceptive activity) induced potent anti-nociceptive effect by co-administration of morphine and tramadol. Identification of new strategies that can potentiate analgesic effects of opioids will be good therapeutic approaches for pain relief. To this aim, male mice were cannulated in the left ventricle by a stereotaxic instrument. A tail-flick test was used to record the pain threshold. The results revealed that intracerebroventricularly injection of morphine induced an anti-nociceptive effect in non-sensitized and morphine-sensitized mice. We found that infusion of tramadol produced an anti-nociceptive response in non-sensitized mice, whereas tramadol in doses of 0.5 and 1 µg/mouse induced analgesia in morphine-sensitized mice. Co-injection of a non-effective dose of tramadol or morphine (0.25 µg/mouse) with different doses of morphine or tramadol (0.25, 0.5, and 1 µg/mouse) respectively potentiated the analgesic effect of the previous drug. An isobolographic analysis of data was performed, indicating a synergistic interaction between morphine and tramadol in non-sensitized and morphine-sensitized mice. Our data indicated that both morphine and tramadol elicit more anti-nociceptive response in morphine sensitized mice; there is a synergistic effect between morphine and tramadol upon induction of analgesic effect in non-sensitized and morphine-sensitized mice. © 2021, Nencki Institute of Experimental Biology. All rights reserved.
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