Abstract
Multimodal analgesic approaches to manage acute and chronic pain are commonly used in humans. Here, we attempted to characterize a synergistic interaction between fentanyl, tramadol, and paracetamol on the inhibition of nociception in a model of visceral pain in mice. The three-drug combined treatment displayed a potent synergistic antinociceptive effect, together with a significant reduction of gastrointestinal transit inhibition. Furthermore, selective μ- and κ-opioid receptor antagonists reversed these synergistic antinociceptive effects, thus suggesting a pivotal role of the opioid system. Overall, this study presents accurate pre-clinical data that might be useful to improve the clinical management of opioid-mediated analgesia.
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