ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

O objetivo deste trabalho foi avaliar o efeito do extrato aquoso das folhas de Erythrina vellutina (AE) sobre ducto deferente de rato. Nesta preparação, o AE inibiu as contrações induzidas por estímulo elétrico de campo de maneira dependente da concentração. Esta inibição não foi afetada após atropina (10-5M), propanolol (10-5M), prazosin (10-5M) ou yohimbina (10-5M), sugerindo uma ação indireta do AE sobre receptores colinérgicos ou adrenérgicos. A incubação da preparação com os antagonistas de canais de K+, tetraetilâmonio (10-6M) ou 4-aminopiridina (10-6M) não alterou o efeito inibitório induzido pelo AE. Entretanto, a glibenclamida (10-6M) atenuou significantemente este efeito, sugerindo um possível envolvimento de canais de K+ dependentes de ATP. Além disso, o AE (0.15 mg/mL) não alterou as contrações induzidas por noradrenalina (10-5M), ATP (10-4M) ou KCl (80 mM), descartando uma interação do AE com um sítio pós-sináptico. Em conclusão, estes resultados demonstram que o efeito inibitório do AE pode ser devido a uma interação pré-sináptica com canais de K+ dependentes de ATP em neurônios simpáticos de ducto deferente de rato.

The effect of the Aqueous Extract from the leaves of Erythrina vellutina (AE) on rat vas deferens preparation was evaluated in this work. The AE inhibited the muscle contractions induced by electrical field stimulation (EFS) in a concentration-dependent manner. This inhibition was not affected by atropine (10-5M), propanolol (10-5M), prazosin (10-5M) or yohimbine (10-5M), suggesting that there is no direct interaction of the AE with cholinergic nor adrenergic receptors. Incubation of vas deferens with the K+ channel antagonists, tetraethylamonium (10-6M) or 4-aminopyridine (10-6M) had also no effect on the AE-induced inhibition. On the other hand, glibenclamide (10-6) significantly attenuated the effect of the AE, suggesting a possible involvement of ATP-dependent K+ channels. The AE (0.15 mg/mL) did not alter the contractions induced by noradrenaline (10-5M), ATP (10-4M) nor KCl (80 mM), against an interaction of the extract with post-synaptic sites. The data presented suggests that the inhibition of the electrically driven muscle twitches by the AE could be due to a pre-synaptic interaction of the extract with ATP-dependent K+ channels from vas deferens sympathetic neurons.

Este trabalho descreve o efeito antinociceptivo e a toxicidade aguda do extrato aquoso das folhas da Hyptis fruticosa Salmz. ex Benth. (Lamiaceae). O extrato aquoso liofilizado, administrado por via oral, reduziu as contorções abdominais induzidas por ácido acético (200, 400 e 500 mg/kg) e o tempo de reação dos animais na primeira fase do teste da formalina (100 mg/kg e 400 mg/kg). No teste da placa quente, o extrato aquoso aumentou o tempo de latência ao calor (100 e 200 mg/kg) tendo este efeito sido revertido pelo antagonista opióide naloxona (5 mg/kg; i.p.). No ensaio de toxicidade aguda, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (v.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da Hyptis fruticosa apresenta efeito antinociceptivo em camundongos e não apresenta toxicidade aguda nas doses testadas.

The antinociceptive effect and the acute toxicity of Hyptis fruticosa leaves were evaluated through the administration of its aqueous extract in mice. The extract, administered orally (200, 400, and 500 mg/kg), reduced the nociceptive response in the writhing test as well as in the early phase of the formalin test (100 and 400 mg/kg) and it increased the latency time in the hot plate test (100 and 200 mg/kg). The antinociceptive effect was reversed by naloxone (5 mg/kg, i.p.). Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Hyptis fruticosa showed no acute toxicity at the evaluated doses and revealed antinociceptive effect in mice. Such effects are possibly associated with the opioid system activation.