Abstract This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Abstract We aimed to evaluate the orofacial antinociceptive effect of geraniol in mice and its molecular anchorage mechanism. Seven mice per group (probabilistic sample) were treated with geraniol (12.5, 25 and 50 mg/kg, i.p.), morphine (6 mg/kg, i.p.) and vehicle (saline + Tween 80 at 0.2%, i.p.) 30 minutes prior to the beginning of the experiment. Injecting glutamate (25 μM), capsaicin (2.5 μg) and formalin (2%) into the right upper lip (perinasal) of the mouse induced nociception. Behavioral analysis of the animals considered the friction time (in seconds) of the mentioned region using hind or front paws by a researcher blinded to the treatment groups. The statistical analysis was performed blindly, considering α = 5%. The results showed that in the glutamate and capsaicin tests, concentrations of 25 mg/kg and 50 mg/kg presented antinociceptive activity (p < 0.005, power> 80%). In the formalin test, geraniol was able to reduce nociception at a concentration of 50 mg/kg (p < 0.005, power> 80%). In the molecular anchorage study, high values of binding between the evaluated substance and receptors of glutamate were observed (metabotropic glutamate receptor, -87.8501 Kcal/mol; N-methyl-D-aspartate, -86.4451 Kcal/mol; α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, -85.6755 Kcal/mol). Geraniol presented orofacial antinociceptive activity, probably by interacting with glutamate-related receptors.

A fibromialgia é uma síndrome dolorosa crônica que afeta até 5% da população mundial. Pode associar-se com distúrbios do sono, do humor e fadiga, e cursar com incapacidade funcional. Sua patogênese envolve distúrbio de modulação central da dor, comprometimento do sistema inibitório descendente e hiperatividade da substância P. Em função da vasta sintomatologia apresentada pelos pacientes e da natureza multifatorial da sua patogênese, seu tratamento ideal requer uma abordagem multidisciplinar incluindo a associação de terapia farmacológica e não farmacológica. A terapia farmacológica atualmente preconizada nessa síndrome inclui, entre outros compostos, antidepressivos, moduladores dos canais de cálcio, relaxantes musculares e analgésicos. O tratamento não farmacológico é realizado, na maioria dos casos, por meio de educação do paciente, atividade física aeróbica supervisionada e terapia cognitivo-comportamental. No entanto, muitos pacientes não apresentam respostas satisfatórias ou apresentam efeitos colaterais associados ao uso dos fármacos a longo prazo, além de referirem dificuldades em permanecer em uma terapia baseada em exercícios e medicina física. Há, portanto, um crescente interesse por parte dos médicos e pacientes por uma terapia alternativa e complementar na fibromialgia. Nesta revisão, os autores discorrem sobre as diversas modalidades terapêuticas empregadas nessa doença, enfatizando as evidências da terapia não farmacológica e do uso de medicina alternativa e complementar nesses pacientes.

Fibromyalgia is a chronic painful syndrome that affects up to 5% of the world population. It is associated with sleep and mood disorders, fatigue, and functional disability. Its pathogenesis involves a disorder of the central modulation of pain, impairment of the descending inhibitory system, and hyperactivity of substance P. Because of the extensive symptomatology of patients with fibromyalgia and its multifactorial pathogenesis, its ideal treatment requires a multidisciplinary approach including the association of pharmacological and non-pharmacological therapies. The pharmacological therapy currently recommended for the syndrome includes antidepressants, calcium-channel modulators, muscle relaxants, and analgesics. In most cases, the non-pharmacological treatment consists of patient education, supervised aerobic physical activity, and cognitive-behavioral therapy. However, many patients do not respond satisfactorily, or have side effects associated with the long-term use of drugs, in addition to reporting difficulties in adhering to a therapy based on exercises and physical medicine. Thus, physicians and patients are increasingly interested in an alternative and complementary therapy for fibromyalgia. This review approaches the different therapeutic modalities used in fibromyalgia, emphasizing the evidence of non-pharmacological therapy and use of alternative and complementary medicine for these patients.

Mikania glomerata é uma planta utilizada na medicina popular, cujas folhas possuem flavonóides e cumarina. Essas substâncias, segundo a literatura, interferem na fertilidade de cães e ratas, respectivamente. O presente trabalho faz um estudo do teste do letal dominante com M. glomerata em ratos Wistar. Animals adultos foram tratados com 1 mL de extrato hidroalcoólico de M. glomerata na dose de 3.3 g/kg de peso corporal durante 52 dias. Os animais foram acasalados com fêmeas não tratadas por sete semanas (grupo 1) ou uma semana antes do início do tratamento e na semana seguinte ao término do mesmo (grupo 2). As variáveis analisadas foram: números de embriões implantados, reabsorções e corpos lúteos, índices de acasalamento, gestação, perda pré-implantação, implantação e reabsorção (grupo 1); número de filhotes nascidos e de animais desmamados (grupo 2). A administração de M. glomerata não interferiu com a fertilidade dos animais e não foram observadas alterações significativas das variáveis analisadas, o que sugere a ausência de efeito mutagênico em ratos Wistar por parte dessa planta.

This work makes an assessment of the dominant lethality of Mikania glomerata in male Wistar rats. Adult male received 1 mL of M. glomerata hydroalcoholic extract at a dose level of 3.3 g/kg body weight for 52 days and were mated with untreated females for seven weeks (group 1) or one week prior to the beginning of treatment and on the week following the end of treatment (group 2). The parameters analyzed were: number of implanted embryos, resorptions and corpora lutea; mating, gestation, preimplantation loss, implantation and resorption indexes (group 1); number of offspring and weaning animals (group 2). The administration of M. glomerata did not show any impairment of fertility and no significant difference in the parameters analyzed, suggesting an absence of mutagenic effect on Wistar rats.