Avaliação da atividade antinociceptiva da α-(fenilseleno)acetofenona em camundongos

Abstract

The feeling of pain is a condition that affects daily, thousands of people around the world and, still yet, it does not exists a completely efficient treatment to this condition, a treatment which does not leads to side effects. So, it is of great importance the search for new molecules that can be applied for the treatment of pain and that does not present many side effects. Thus, the chemical element selenium has been a target of interest for many research groups due its pharmacological and biological properties. Therefore, the aim of this study was to evaluate the antinociceptive activity of the organoselenium compound, α- (phenylalanyl) acetophenone (PSAP) in mice and also, to elucidate the mechanism that could be possibly involved with the antinociceptive activity of the compound. Objectifying the assessment of the possible antinocicpetive action of PSAP, two nociception assays where realised, the glutamate and the formalin tests, which are both chemical nociception inductors. The intragastric administration (i.g.) of PSAP (10 – 50 mg/Kg) has prevented the nociception, induced by the intraplantar (i.pl.) injection of formalin (20μL), in the neurogenic phase. Also, PSAP was effective in reducing paw oedema formation. As well as in the neurogenic phase, in the inflammatory phase, PSAP (1 – 50 mg/Kg, i.g.) has reduced paw licking, induced by formalin (i.pl.). Besides that, PSAP (0.1 - 50 mg/Kg, i.g.) has also diminished the licking time of the paw in the glutamate test, showing a reduction in the nociception induced by glutamate administration(20 μL, i.pl.) in mice. The contribution of the serotoninergic, dopaminergic and noradrenergic systems to the antinociceptive activity of PSAP (1 mg/Kg, i.g.) was assessed by the glutamate nociception induced test. Mice pre-treatment with sulpiride (5 mg/Kg, i.p., a D2 and D3 dopaminergic receptors antagonist), prazosin (0.15 mg/Kg, i.p., an α1adrenoreceptor antagonist) and yoimbine (1 mg/Kg, i.p., an α2 adrenoreceptor antagonist), blocked the antinociceptive effect cause by PSAP. Conversely, SCH23390 (0.05 mg/Kg, i.p., a D1 receptor antagonist), WAY100635 (0.7 mg/Kg, i.p., a selective 5-HT1areceptor antagonist), ketanserin (0.3 mg/Kg, i.p., a selective 5-HT2a receptor antagonist) and ondansetron (0.5 mg/Kg, i.p., a selective 5-HT3receptor antagonist) did not change the antinocieptive effect of PSAP (1mg/Kg, i.g.) in the glutamate test performed in mice. These results indicate that PSAP antinociceptive action can be related to its interaction with dopaminergic and noradrenergic systems. Also, it was assessed mice locomotor activity through the open field test. It was observed that the administrations of PSAP, antagonists and the interaction between PSAP and antagonist did not modified the number of crossings of the animal in the open field apparatus. This present study has demonstrated that PSAP has antinociceptive action and it can be assumed that this action is related to its involvement with the dopaminergic and adrenergic systems.