Evidências científicas sobre o efeito antinociceptivo de produtos naturais e (-)-mirtenol em modelos de dor orofacial

• Ano de defesa: 2019
• Autor(a) principal: Oliveira, Janaíne Prata de
• Orientador(a): Camargo, Enilton Aparecido
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Dor orofacial; Desordens temporomandibulares; Produtos naturais; Mirtenol; Neuroinflamação; Terpenos; Revisão sistemática
• Palavras-chave em Inglês: Orofacial pain; Temporomandibular disorders; Natural products; Myrtenol; Neuroinflammation; Terpene; Systematic review
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/12594

Orofacial pain is located in head and neck regions and is considered a healthy public problem that is present in 10-25% of the global population. Many natural products, especially terpenes, have been used in pre-clinical studies that mimick these conditions, which suggests an alternative for the orofacial pain management. (-)-Myrtenol possesses anti-inflammatory and analgesic properties, but no description is available about its effect on orofacial region. The goals of this study were to conduct two systematic reviews of preclinical studies about the effectiveness of natural products, one involving orofacial pain models and another involving models of temporomandibular disorders (TMD), as well as to investigate the effect of myrtenol on orofacial inflammation and nociception in orofacial region of mice. The searches for the systematic reviews was performed on MEDLINE, Web of Science, SCOPUS, EMBASE, LILACS, SCIELO and Schoolar Google. Two independent reviewers made the selection of relevant studies, data extraction and risk of bias evaluation. In the first review, the studies that used natural products on orofacial pain models were selected and outcomes were compared to control group (placebo). Twenty-eight studies were selected, analyzed individually and disposed on a descriptive table. Nine studies that used terpenes participated of quantitative analysis by the indirect treatment comparison (ITC). The qualitative results showed the effectiveness of the natural products in orofacial pain induced by chemical agents. In ITC analysis, (-)-linalool, citronellol, p-cimene and carvacrol were considered superior to other terpenes in the tests of formalin (first and second phases), capsaicin and glutamate, respectively.In the second systematic review, studies with natural products as interventions on TMD experimental models were eligible. Thirteen studies underwent qualitative analysis All natural products used were effective in these models. For the experimental study, we evaluated the in vitro viability of glioma-type cells C6 (GC6) by MTT test in the presence of different concentrations of myrtenol. For in vivo experiments, it was used Swiss mice male (CEPA/UFS 19/2018) that received pre-treatment with myrtenol (12.5, 25 and 50 mg/kg) or vehicle (saline +Tween 80 at 0.2%) or positive controls (morphine at 5 mg/kg and indomethacin at 10 mg/kg) 30 minutes before orofacial inflammation or nociception induction. The inflammation in masseter muscle was induced by carragenan (3%) injection, i.m. Six hours after induction, animals were euthanized and their tissue were collected for myeloperoxidase (MPO) analysis and histological analysis on muscle and interleukin (IL)-1β, tumoral necrosis factor (TNF)-α and IL-6 concentrations on trigeminal ganglia and nucleus. The orofacial nociception was induced by formalin injection in upper lip of mice and the nociceptive behavior was mensured during the first (0-5 min) and second phase (15-40 min) of test. Immediately after the test, animals were perfused, euthanized and their brain and trigeminal ganglion were collected for imunohistochemistry for MAPK P-p38. The treatment with myrtenol did not alter GC6 viability, but it reduced MPO activity and other inflammatory parameters in masseter muscle and IL-1β levels in trigeminal ganglion and nucleus and TNF-α in trigeminal ganglion. It also reduced nociceptive behavior on formalin test, due in part to the decrease of MAPK-p38. In summary, we showed that myrtenol causes anti-inflammatory and antinociceptive effects in orofacial region by modulating responses in the masseter muscle or in neural structures, which agrees with the effects of many natural products selected in the systematic reviews that decreased relevant outcomes in preclinical models of orofacial pain and TMD.