Evaluation of the orofacial antinociceptive profile of the ethyl acetate fraction and its major constituent, rosmarinic acid, from the leaves of Hyptis pectinata on rodents

ABSTRACT Hyptis pectinata (L.) Poit., Lamiaceae, popularly known as "sambacaitá," is an aromatic shrub largely grown in the Brazilian northeastern. We investigated the antinociceptive effects of the ethyl acetate fraction obtained from the leaves of H. pectinata and of its main constituent rosmarinic acid, on formalin (2%)-, glutamate (25 µM)- and capsaicin (2.5 µg)-induced orofacial nociception in rodents. Male mice were pretreated with ethyl acetate fraction (100, 200 or 400 mg/kg, p.o.), rosmarinic acid (10 or 20 mg/kg, p.o.), morphine (5 mg/kg, i.p.), or vehicle (distilled water + 0.2% Tween 80). Ethyl acetate fraction reduced the nociceptive face-rubbing behavior during the two phase of the formalin test, whereas pretreatment with rosmarinic acid decreased the pain behavior in the second phase. Ethyl acetate fraction produced significant antinociceptive effects in the capsaicin and glutamate tests. This study showed that oral administration of ethyl acetate fraction produced potent antinociceptive effects compared to treatment with rosmarinic acid.

Phytochemical screening, antinociceptive and anti-inflammatory effects of the essential oil of Myrcia pubiflora in mice

This report aimed to investigate the chemical composition and possible antinociceptive and anti-inflammatory effects of the essential oil from fresh leaves of Myrcia pubiflora DC., Myrtaceae (EOMP), through different experimental tests. The essential oil of M. pubiflora (EOMP) was obtained by hydrodistillation, analyzed by GC-MS, and tested at doses of 25, 50, and 100 mg/kg (i.p.) in three different tests of nociception (acetic acid-induced writhing test, formalin test, and hot plate test) and one test of inflammation (leukocyte migration to the peritoneal cavity) in order to evaluate the motor activity in mice treated with EOMP. The major component of EOMP was caryophyllene oxide (22.16 percent). This oil significantly reduced the number of writhes in an acetic acid test and the time spent licking the paw at the second phase of the formalin test. Furthermore, EOMP inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. However, administration of EOMP did not alter reaction time in the hot plate test, and did not affect the motor coordination test. These results indicate antinociceptive and anti-inflammatory properties of EOMP probably mediated via inhibition of inflammatory mediator synthesis or other peripheral pathway.

Ocimum basilicum leaf essential oil and (-)-linalool reduce orofacial nociception in rodents: a behavioral and electrophysiological approach

The present study investigated the antinociceptive effects of Ocimum basilicum L. (Lamiaceae) leaf essential oil (LEO) and (-)-linalool (LIN) in formalin (2 percent)-, glutamate (25 µM)- and capsaicin (2.5 µg)- induced orofacial nociception models in mice. The involvement of these substances was further evaluated on the neuronal excitability of the hippocampal dentate gyrus. Male mice (n=8/group) were pretreated separately with LEO and by LIN (50, 100, and 200 mg/kg, i.p.), morphine (5 mg/kg, i.p.) and vehicle (saline + Tween 80 0.2 percent), before injection of nociceptive agent into the right upper lip (perinasal area). The LEO and LIN reduced the nociceptive face-rubbing behaviour in both phases on formalin test. LEO and LIN, at high doses, produced significantly antinociceptive effect in the capsaicin and glutamate tests. In hippocampal slices, LEO inhibited the population spike generated by stimulation of the hylus (antidromic stimulation), with an IC50 of 0.1±0.05 mg/mL. This response was reversibly blocked by lidocaine (0.5 mg/mL), a known voltage-dependent sodium channel antagonist and by LIN (0.5 mg/mL). Our results suggest that LEO and LIN modulate neurogenic and inflammatory pain in the tests of orofacial nociception induced by formalin, capsaicin and glutamate. Part of these effects may be associated with decreased peripheral and central neuronal excitability.

p-Cymene reduces orofacial nociceptive response in mice

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2 percent Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

Variabilidade interobservadores no diagnóstico de lesões precursoras do câncer anal: estudo do cenário habitual / Interobserver variability in the diagnosis of anal cancer precursor lesions: study of the usual scenario

OBJETIVO: Analisar a variabilidade interobservadores no diagnóstico de lesões precursoras do câncer anal no cenário mais comum de um serviço constituído por patologistas sem experiência prévia no diagnóstico destas lesões. MÉTODOS: Quinhentas e duas lâminas histopatológicas com espécimes anais retirados de 372 pacientes HIV-positivos e HIV-negativos foram analisadas no Departamento de Patologia da Fundação de Medicina Tropical do Amazonas por três patologistas com ampla experiência no diagnóstico de doenças tropicais e infecciosas, mas sem experiência prévia importante no diagnóstico de lesões precursoras do câncer anal. As leituras individuais de cada patologista foram comparadas com a que se seguiu a diagnóstico de consenso em microscópio de ótica compartilhada. Os diagnósticos individuais foram confrontados com os de consenso mediante análise da estatística kappa. RESULTADOS: A concordância absoluta entre cada diagnóstico individual e o de consenso correspondente foi ruim (kappa=-0,002). Considerando os resultados apenas positivos ou negativos para lesões intraepiteliais escamosas anais, obteve-se concordância regular entre os observadores (kappa=0,35), enquanto que a concordância foi moderada quando os resultados histopatológicos foram considerados positivos ou negativos para lesão intraepitelial de alto grau ou câncer (kappa=0,52). CONCLUSÃO: A variabilidade interobservadores no diagnóstico histopatológico do câncer anal e de suas lesões precursoras entre patologistas sem grande experiência na área, apesar de experts em outras, é tal que os diagnósticos neste campo e neste cenário comum devem sempre ser de consenso.

OBJECTIVE: To assess interobserver variability in the diagnosis of anal cancer precursor lesions in the usual scenario of a service consisting of pathologists without previous experience in the diagnosis of these lesions. METHODS: Five hundred and two anal specimens taken from 372 HIV-positive and HIV-negative patients were analyzed at the Pathology Department of the Tropical Medicine Foundation of Amazonas by three pathologists with extensive experience in the diagnosis of infectious and tropical diseases, but without significant prior experience in the diagnosis of anal cancer precursor lesions. The individual readings of each pathologist were compared to the one following the consensus diagnosis in shared optical microscope by kappa statistics. RESULTS: The absolute agreement between each individual diagnosis and corresponding consensus was poor (kappa = -0.002). Considering only the positive or negative results for anal squamous intraepithelial lesions, we obtained a fair agreement between observers (kappa = 0.35), while the agreement was moderate when the histopathological findings were considered positive or negative for high-grade squamous intraepithelial lesion or cancer (kappa = 0.52). CONCLUSION: The interobserver variability in histopathologic diagnosis of anal cancer and its precursor lesions among pathologists with little experience in the area is such that the diagnoses in this field and this scenario should always be a consensus.

Bioassay-guided evaluation of central nervous system effects of citronellal in rodents

The central nervous system (CNS) depressant and anticonvulsant activities of citronellal (CT) were investigated in animal models. The CT in doses of 100, 200 and 400 mg/kg injected by i.p. route in mice caused a significant decrease in the motor activity of animals when compared with the control group. The highest dose of CT significantly reduced the remaining time of the animals on the Rota-rod apparatus up to 2 h. Additionally, CT at doses 100, 200 and 400 mg/ kg (i.p.) was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). It was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200 and 400 mg/kg, resulting in 30 and 40 percent of protection, respectively. This compound was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 400 mg/kg. In the same way, the anticonvulsant effect of CT was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities.

Citral reduces nociceptive and inflammatory response in rodents

Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8 percent) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

Anti-inflammatory and redox-protective activities of citronellal

The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.

Antinociceptive and anti-inflammatory effects of the essential oil of Eugenia candolleana DC., Myrtaceae, on mice / Efeito antinociceptivo e antiinflamatório do óleo essencial de Eugenia candolleana DC. (Myrtaceae) em roedores

Eugenia candolleana DC. (Myrtaceae), commonly known as "murta" or "murtinha", is a plant species without any chemical or pharmacological study described in the literature. It has been popularly used for the treatment of pain and fever. This report aimed to investigate the possible antinociceptive and anti-inflammatory effects of the essential oil extracted from fresh leaves of Eugenia candolleana DC. (EOEc) in rodents. Following intraperitoneal injection, EOEc (25, 50 and 100 mg/kg) reduced the number of writhes significantly in a writhing test and the number of paw licks during phase two of formalin test (p < 0.001). However, administration of EOEc did not alter the time of reaction in hot plate test. Furthermore, EOEc inhibited (p < 0.01) the carrageenan-induced leukocyte migration to the peritoneal cavity. These results indicate antinociceptive and anti-inflammatory properties of EOEc probably mediated via inhibition of prostaglandin synthesis or other peripherally pathway.

Eugenia candolleana DC. (Myrtaceae), conhecida popularmente como "murta" ou "murtinha", é uma espécie vegetal sem estudos químicos e farmacológicos descritos na literatura, distribuída no Nordeste brasileiro, principalmente, na Zona da Mata. Na medicina popular do Estado de Sergipe é utilizada no tratamento de distúrbios febris e da dor. O presente estudo buscou avaliar as possíveis atividades antinociceptiva e antiinflamatória do óleo essencial extraído das folhas de E. candolleana DC (OEEc) em roedores. A administração intraperitoneal (i.p.) do OEEc (25, 50 e 100 mg/kg) reduziu significativamente o número de contorções no teste das contorções abdominais e a duração da lambida da pata na segunda fase do teste da formalina (p < 0,001). Entretanto, a administração do OEEc não alterou o tempo de reação no teste da placa quente. No experimento de peritonite induzido por carragenina, o OEEc reduziu de forma significativa (p < 0,01) a migração de leucócitos para a cavidade peritoneal. Os resultados obtidos sugerem que o OEEc possui ação antinociceptiva, provavelmente mediado por mecanismos periféricos, e ação antiinflamatória.

Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission / Propriedade anticonvulsivante de N-saliciloiltriptamina: proteção significativa com o sistema GABAérgico

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40 percent of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABA A-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.

OBJETIVO: O presente estudo buscou avaliar o possível efeito anticonvulsivante do novo análogo da triptamina, N-saliciloiltriptamina (NST), em roedores. MÉTODOS E RESULTADOS: Na avaliação do efeito anticonvulsivante, os animais tratados com NST (100 e 200 mg/kg, i.p.) foram protegidos de maneira estatisticamente significativa (p<0,05) quanto a latência e incidência do aparecimento das convulsões induzidas pela administração do pentilenotetrazol (PTZ) e da picrotoxina (PIC). O efeito protetor do NST nas convulsões induzidas pelo PTZ foi revertido pela administração do flumazenil (10 mg/kg, i.p.), um antagonista dos receptores GABA-benzodiazepínicos (GABA A-BZD). A administração de NST (100 e 200 mg/kg, i.p.) protegeu de forma estatisticamente significativa (p < 0,05) os animais no teste das convulsões induzidas pelo eletrochoque-auricular em camundongos. CONCLUSÃO: Os resultados do presente estudo sugerem que o efeito anticonvulsivante de NST está associado, pelo menos em parte, ao sistema GABAérgico.