Synergistic interaction between fentanyl and a tramadol:Paracetamol combination on the inhibition of nociception in mice

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. © the japanese pharmacological society.