O envolvimento do sistema endocanabinóide no efeito antihiperalgésico da inalação do óleo essencial Cedrus Atlântica em um modelo pré-clínico de dor pós-operatória
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Data
2021
Tipo de documento
Dissertação
Título da Revista
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Título de Volume
Área do conhecimento
Ciências da Saúde
Modalidade de acesso
Acesso aberto
Editora
Autores
Emer, Aline Armiliato
Orientador
Martins, Daniel Fernandes
Coorientador
Resumo
O presente estudo teve como objetivo investigar o envolvimento do sistema endocanabinóide no efeito antihiperalgésico da inalação do óleo essencial Cedrus atlantica (OECa) em um modelo pré-clínico de dor pós-operatória. Inicialmente foram caracterizados os constituintes do OECa pela análise fitoquímica por meio de cromatografia gasosa acoplada a espectrometria de massa. Os experimentos comportamentais foram conduzidos após a aprovação pelo Comissão de Ética no Uso de Animais da UNISUL - CEUA/UNISUL (13.012.4.08.IV). Nestes experimentos foram utilizados camundongos Swiss machos pesando de 25 a 35 g. Para indução da dor pós-operatória os animais foram submetidos a uma cirurgia de incisão plantar (CIP) na pata traseira direita. Vinte e quatro horas após, os animais inalaram o OECa por diferentes períodos de tempos (1, 5, 30 e 60 minutos). A hiperalgesia mecânica foi avaliada utilizando o monofilamento de von Frey (0,4g) até o fim do efeito antihiperalgésico do OECa. Também foi verificado o efeito da inalação diária, durante 6 dias e o efeito per se do OECa. Para avaliar o envolvimento do sistema endocanabinóide foram utilizadas 2 abordagem diferentes: uma por meio de antagonistas para os receptores CB1 e CB2, administrados em diferentes sítios (intraperitoneal [i.p.], intraplantar [i.pl.] e intratecal [i.t.]). E outra por meio da avaliação do efeito sinérgico de inibidores da degradação de endocanabinóides. Nos resultados da análise fitoquímica identificou-se vinte e um elementos constituintes. Dentre os compostos encontrados, os hidrocarbonetos sesquiterpenos ?- himachaleno (16,6%), ?-himachaleno (10,4%) e ?-himachaleno (46,4%) foram os compostos majoritários. Nos testes comportamentais notou-se que a inalação do OECa por 30 e 60 minutos induziu efeito antihiperalgésico por até 2 horas. Em contraste, a inalação do OECa por apenas 1 minuto não induziu mudanças no limiar sensorial dos animais. A inalação diária do OECa diminuiu significativamente a hiperalgesia mecânica, até o quinto dia. Na avaliação do efeito per se, não houve alterações do limiar sensorial. Em relação a análise do envolvimento do sistema endocanabinóide verificou-se que as administrações sistêmica e central (i.t.) dos antagonistas AM281 e AM630, para os receptores canabinóides CB1 e CB2, respectivamente, preveniram o efeito antihiperalgésico do OECa; a administração de uma dose sub-efetiva dos inibidores da degradação de endocanabinóides (Amido hidrolase de ácidos graxos [FAAH] que degrada anandamida e da lipase mono acil glicerol [MAGL] que degrada o 2-araquidonil glicerol) com a subsequente inalação do OECa por 1 minuto, prolongou o efeito antihiperalgésico do OECa por até 7 horas. Assim, pôde-se concluir que o mecanismo pelo qual o OECa exerce seu efeito pode ser por modular a atividade destas enzimas e assim influenciar na sinalização endocanabinoidérgica. Estes resultados demonstram pela primeira vez na literatura, o envolvimento do sistema endocanabinóide no efeito antihiperalgésico do OECa, em um modelo pré-clínico de dor pós-operatória.
The present study investigated the involvement of the endocannabinoid system in the antihyperalgesic effect induced by the inhalation of the essential oil Cedrus atlantica (OECa) in a preclinical model of postoperative pain. Initially, the constituents of the OECa were phytochemically characterized by Gas chromatography-mass spectrometry (GC-MS). The behavioral experiments were conducted after approval by the Ethics Committee on Animal Use - CEUA/UNISUL (13.012.4.08.IV). In these experiments Swiss male mice weighing 25 to 35 g were used. For induction of post-operative pain the animals underwent a surgical plantar incision (CIP) in the right hind paw. Twenty-four hours later, the animals inhaled OECa for different periods of time (1, 5, 30 and 60 minutes). Mechanical hyperalgesia was assessed using a von Frey monofilament (0.4g) until the antihyperalgesic effect of OECa was over. The effect of daily inhalation (for 6 days) and the effect of OECa per se were also observed. To assess the involvement of the endocannabinoid system 2 different approaches were used: (1) by administering antagonists for the CB1 and CB2 receptors in different sites (intraperitoneal [i.p.], intraplantar [i.pl.] and intrathecal [i.t.]) and (2) by assessing the synergistic effect of the inhibitors of the degradation of endocannabinoids. The results of the phytochemical analysis identified twenty-one constituents, among which the hydrocarbons ?- himachalene (16,6%), ?-himachalene (10,4%) e ?-himachalene (46,4%) were the main components. The behavioral tests demonstrated that the inhalation of OECa for 30 and 60 minutes induced an antihyperalgesic effect that lasted for up to 2 hours. In contrast, inhalation of OECa for only 1 minute did not induce changes in the sensory threshold of the animals. Daily inhalation of OECa significantly reduced mechanical hyperalgesia until the fifth day. The administration of OECa per se did not induce any changes to the animal's sensory threshold. Regarding the involvement of the endocannabinoid system, the results demonstrated that systemic and central (i.t.) administration of the antagonists AM281 and AM630 for the cannabinoid receptors CB1 and CB2, respectively, prevented the antihyperalgesic effect of OECa; the administration of a sub-effective dose of the inhibitors of the degradation of endocannabinoids (Fatty acid amide hydrolase [FAAH] which degrades anandamide and Monoacylglycerol lipase [MAGL] which degrades 2-arachidonoyl glycerol) with subsequent inhalation of OECa for 1 minute, prolonged the antihyperalgesic effect of OECa for up to 7 hours. Thus, it was concluded that the mechanism by which OECa exerts its effect might be by modulating the activity of these enzymes and thus influencing endocannabinoid signaling. These results demonstrate for the first time the involvement of the endocannabinoid system in the antihyperalgesic effect of OECa in a preclinical model of postoperative pain.
The present study investigated the involvement of the endocannabinoid system in the antihyperalgesic effect induced by the inhalation of the essential oil Cedrus atlantica (OECa) in a preclinical model of postoperative pain. Initially, the constituents of the OECa were phytochemically characterized by Gas chromatography-mass spectrometry (GC-MS). The behavioral experiments were conducted after approval by the Ethics Committee on Animal Use - CEUA/UNISUL (13.012.4.08.IV). In these experiments Swiss male mice weighing 25 to 35 g were used. For induction of post-operative pain the animals underwent a surgical plantar incision (CIP) in the right hind paw. Twenty-four hours later, the animals inhaled OECa for different periods of time (1, 5, 30 and 60 minutes). Mechanical hyperalgesia was assessed using a von Frey monofilament (0.4g) until the antihyperalgesic effect of OECa was over. The effect of daily inhalation (for 6 days) and the effect of OECa per se were also observed. To assess the involvement of the endocannabinoid system 2 different approaches were used: (1) by administering antagonists for the CB1 and CB2 receptors in different sites (intraperitoneal [i.p.], intraplantar [i.pl.] and intrathecal [i.t.]) and (2) by assessing the synergistic effect of the inhibitors of the degradation of endocannabinoids. The results of the phytochemical analysis identified twenty-one constituents, among which the hydrocarbons ?- himachalene (16,6%), ?-himachalene (10,4%) e ?-himachalene (46,4%) were the main components. The behavioral tests demonstrated that the inhalation of OECa for 30 and 60 minutes induced an antihyperalgesic effect that lasted for up to 2 hours. In contrast, inhalation of OECa for only 1 minute did not induce changes in the sensory threshold of the animals. Daily inhalation of OECa significantly reduced mechanical hyperalgesia until the fifth day. The administration of OECa per se did not induce any changes to the animal's sensory threshold. Regarding the involvement of the endocannabinoid system, the results demonstrated that systemic and central (i.t.) administration of the antagonists AM281 and AM630 for the cannabinoid receptors CB1 and CB2, respectively, prevented the antihyperalgesic effect of OECa; the administration of a sub-effective dose of the inhibitors of the degradation of endocannabinoids (Fatty acid amide hydrolase [FAAH] which degrades anandamide and Monoacylglycerol lipase [MAGL] which degrades 2-arachidonoyl glycerol) with subsequent inhalation of OECa for 1 minute, prolonged the antihyperalgesic effect of OECa for up to 7 hours. Thus, it was concluded that the mechanism by which OECa exerts its effect might be by modulating the activity of these enzymes and thus influencing endocannabinoid signaling. These results demonstrate for the first time the involvement of the endocannabinoid system in the antihyperalgesic effect of OECa in a preclinical model of postoperative pain.
Palavras-chave
Aromaterapia, Canabinóides, Cuidados pós-operatórios, Dor - tratamento, Sistema nervoso