Efeito do complexo de inclusão contendo Beta-Ciclodextrina e óleo essencial de Lippia Grata (Verbenaceae) na nocicepção orofacial em modelos experimentais

Abstract

The treatment of orofacial pain remains a major challenge for modern medicine. So, new therapeutic proposals has sought in natural products pharmacological options for this nosology. In the current study, it was prepared and physicochemically characterized a β-cyclodextrin complex containing L. grata leaf essential oil (β-CD/EO) in order to investigate their possible antinociceptive activity in animal models of orofacial pain. The essential oil from the leaves of Lippia grata (EO ) was obtained by hydrodistillation in a Clevenger-type apparatus and the main compounds identified was made through CG-MS. The phytochemical analysis of EO demonstred the presence of camphor (28,69%), (E)-caryophillene (11,47%), bicyclogermacrene (10,22%), camphene (9,45%) and borneol (7,64%) as the main compounds. Following these preliminary results, the inclusion complex of β-cyclodextrin and EO (β-CD/EO) was prepared by slurry procedure (SC). It was taken physicochemical characterization. The results of DSC and TG/DTG showed that the products prepared by SC methods were able to incorporate greater amounts of EO. In the X-ray diffractogram, it was showed that complex between EO and -CD was formed. Male Swiss mice were pretreated with β-CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.), or vehicle (distilled water, p.o.), 90 min. before treatment with formalin (20 µl, 2%), capsaicin (20 µl, 2,5 µg), or glutamate (40 μl, 25 μM) into the right upper lip. The obtained data were evaluated by one-way analysis of variance (ANOVA), followed by Tukey’s test. The results demonstrated that p.o. treatment with β-CD/EO was (p<0,05 or p<0,001) capable in reducing the nociceptive face-rubbing behavior in both phases of the formalin test. β-CD/EO-treated mice were also (p<0.05 or p<0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an imunofluorescence protocol for Fos protein. The imunofluorescence protocol demonstrated that the β-CD/EO significantly activated (p<0,05; p<0,01 or p<0,001) the motor cortex, the locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects did not alter, in tested doses, the motor coordination of mice in the rota-rod test. These results suggest that treatment with β-CD/EO induces an analgesic profile in experimental models of orofacial nociception, promising pharmacologic complex in treatment of orofacial pain.