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Previous issue date: 2013-09-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / 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 ?-cyclodextrin complex containing L. grata leaf essential oil (?-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 ?-cyclodextrin and EO (?-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 ?-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 ?l, 2%), capsaicin (20 ?l, 2,5 ?g), or glutamate (40 ?l, 25 ?M) 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 ?-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. ?-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 ?-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 ?-CD/EO induces an analgesic profile in experimental models of orofacial nociception, promising pharmacologic complex in treatment of orofacial pain. / O tratamento da dor orofacial representa um importante desafio para a medicina moderna. Desta forma, novas propostas terap?uticas t?m buscado nos produtos naturais op??es farmacol?gicas para esta nosologia. No presente estudo, foi preparado e caracterizado fisicoquimicamente, um complexo de ?-ciclodextrina incorporado com o ?leo essencial das folhas de Lippia grata (?-CD/OE) buscando avaliar sua poss?vel a??o antinociceptiva em modelos animais de dor orofacial. O ?leo essencial (OE) foi obtido por hidrodestila??o em aparato de Clevenger e os compostos marjorit?rios foram identificados por CG-MS. A an?lise fitoqu?mica do ?leo demonstrou a presen?a de c?nfora (28,69%), (E)-cariofileno (11,47%), biciclogermacreno (10,22%), c?nfeno (9,45%) e borneol (7,64%) como principais componentes. Ap?s estes resultados preliminares, este ?leo foi ent?o complexado em ?-ciclodextrina e a an?lise fisicoqu?mica realizada. Os resultados da DSC e TG/DTG demonstraram que produtos preparados por m?todos de coevapora??o foram capazes de incorporar grandes quantidades de ?leo essencial. No difractograma de raios X, foi mostrado que o complexo entre OE e ?-CD foi formado. Camundongos machos Swiss foram pr?-tratados com ?-CD/OE (6, 12 ou 24 mg/kg, per os, gavagem, v.o.), morfina (5 mg/kg, i.p.), ou ve?culo (?gua destilada, v.o.), 90 min. antes do tratamento com formalina (20 ?l, 2%), capsaicina (20 ?l, 2,5 ?g), ou glutamato (40 ?l, 25 ?M) no l?bio superior direito. Os dados obtidos foram avaliados por an?lise de vari?ncia de uma via (ANOVA), seguido pelo teste de Tukey. Os resultados demonstraram que o tratamento v.o. com ?-CD/OE foi capaz de reduzir (p<0,05 ou p<0,001) o comportamento nociceptivo de co?ar a face em ambas as fases do teste da formalina. Camundongos tratados com ?-CD/OE foram tamb?m (p<0,05 ou p<0,001) protegidos contra a nocicep??o induzida por capsaicina e glutamato. Para avaliar a a??o no sistema nervoso central (SNC), noventa minutos ap?s o tratamento, os camundongos foram perfundidos, os c?rebros coletados, crioprotegidos, cortados num criostato e submetidos a um protocolo de imunofluoresc?ncia para prote?na Fos. O protocolo de imunofluoresc?ncia demonstrou que o complexo de ?-CD/EO ativou (p<0,05; p<0,01 ou p<0,001) o c?rtex motor, o locus ceruleus, o n?cleo magno da rafe e a subst?ncia cinzenta periaquedutal do SNC. Esses efeitos n?o alteraram, nas doses testadas, a coordena??o motora dos camundongos no teste rota-rod. Os resultados sugerem que o tratamento com ?-CD/EO induz perfil analg?sico em modelos experimentais de nocicep??o orofacial, sendo um complexo farmacol?gico promissor no tratamento da dor orofacial.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.uefs.br:8080:tede/255 |
| Date | 27 September 2013 |
| Creators | Lima, Pollyana de Souza Siqueira |
| Contributors | Lucchese, Ang?lica Maria |
| Publisher | Universidade Estadual de Feira de Santana, Mestrado Acad?mico em Biotecnologia, UEFS, Brasil, DEPARTAMENTO DE CI?NCIAS BIOL?GICAS |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UEFS, instname:Universidade Estadual de Feira de Santana, instacron:UEFS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7701973706309601282, 600, 600, 600, 600, -6971480722008537872, -3439178843068202161, 2075167498588264571 |
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