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.
Unit of Pharmacology, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, The University of Barcelona, Spain. vfernandez@ub.edu
Víctor
V
Fernández-Dueñas
Raquel
R
Poveda
Sílvia
S
Sánchez
Francisco
F
Ciruela
D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*; D059265:Visceral Pain / Q000188:drug therapy* / Q000503:physiopathology
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000082:Acetaminophen; D014147:Tramadol; D005283:Fentanyl