Noradrenergic modulation of Dex-ketoprofen analgesia in preclinical orofacial pain

Hugo F Miranda 1, *, Viviana Noriega 2, 3, Francisca Moreno 4, Fernando Sierralta 5, Ramón Sotomayor-Zárate 6 and Juan Carlos Prieto 3, 5

1 Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
2 Faculty of Medicine, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
3 Cardiovascular Department, Clinical Hospital, Universidad de Chile, Santiago, Chile.
4 Faculty of Medicine, Diego Portales University, Santiago, Chile.
5 Pharmacology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
6 Laboratory of Neurochemistry and Neuropharmacology, Faculty of Sciences, Universidad de Valparaíso, Valparaíso, Chile.
 
Research Article
International Journal of Frontiers in Biology and Pharmacy Research, 2022, 03(01), 030–036.
Article DOI: 10.53294/ijfbpr.2022.3.1.0053
Publication history: 
Received on 08 July 2022; revised on 11 August 2022; accepted on 13 August 2022
 
Abstract: 
Dexketoprofen (DEX) is the dextrorotatory enantiomer of S (+) configuration with a high antinociceptive activity of ketoprofen. The aim of this study was to evaluate the pharmacological interaction of DEX with the noradrenergic antagonist's prazosin, yohimbine, propranolol and atenolol in the formalin orofacial pain in mice. Analgesia to nociceptive and inflammatory pain was evaluated by dose response curves to DEX before and after the i.p. administration of 1.0 mg/kg of prazosin, or yohimbine, or propranolol or atenolol. Results are presented as means ± SEM and differences were calculated by one-way ANOVA, followed by Tukey’s post-test. DEX produced a dose-related antinociceptive effect with varying potencies in both trial phases, with prazosin and yohimbine increasing the efficacy of DEX and propranolol and atenolol having no effect. These findings suggests that the increased efficacy of DEX cannot be explained by only inhibition of COXs, since it may be a consequence of multiple pharmacodynamic interactions induced by the activation of a-adrenoceptors in the opioidergic, cannabinoid, nitrergic or serotonergic mechanisms involved in pain. These results indicate that the combination of DEX with prazosin or yohimbine could be a new and effective alternative for the management of pain.
 
Keywords: 
Orofacial pain; Dexketoprofen; Prazosin; Yohimbine; Propranolol; Atenolol
 
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