Influence of bee venom on antinociceptive activity of selected analgesic drugs in hot plate test in mice

Abstract

Introduction and Objective. The aim of the study was to investigate the effect of bee venom on the activity of two analgesics: ketoprofen (a non-steroidal anti-inflammatory drug) and tramadol (an opioid drug) in the acute thermal pain model (hot-plate test) in mice. Materials and Method. Linear regression analysis was used to evaluate the dose-response relationship between logarithms of drug doses and their resultant maximum possible anti-nociceptive effects in the mouse hot-plate test. Doses that increased the anti-nociceptive effect by 20% (ED20 values) for bee venom, ketoprofen and tramadol, and their combination were calculated from linear equations. The interaction between bee venom and the selected anaglesics was evaluated using isobolographic analysis. Results. The study showed that all compounds produced a definite anti-nociceptive effect, and the experimentally-derived ED20 values for bee venom, ketoprofen and tramadol, when applied indivisually, was 3.64 mg/kg, 79.88 mg/kg and 13.26 mg/kg, respectively. Isobolographic analysis revealed that the combination of bee venom and ketoprofen at a fixed ratio of 1:1 was supra-additive (synergistic). The experimentally-derived ED20 mix was 26.33 mg/kg, which significantly differed from the ED20 add of 41.76 mg/kg (p < 0.5). The experimentally-derived ED20 mix of bee venom and tramadol was 2.90 mg/kg, and differed significantly from the theoretically estimated ED20 add of 8.45 mg/kg (p < 0.5), also indicating a synergistic interaction in the hot-plate test in mice. Moreover, none of the tested combinations indicated any adverse effects in the chimney test and the grip-strength test in mice. Conclusions. Overall, the obtained results demonstrated that bee venom significantly increased the anti-nociceptive activity of ketoprofen and tramadol in the hot-plate model of nociceptive pain in mice.