RESUMO
There is increasing evidence that the toll-like receptor 4 (TLR4) signaling pathway contribute to development of hyperalgesia in the trigeminal system. The aim of the present study was to investigate the role of TLR4 in the trigeminal ganglion (TG) in facial hyperalgesia induced by injection of Lipopolysaccharide (LPS) or intraoral mucosal incision, which is an orofacial postoperative pain model, in male Wistar rats. The TLR4 antagonist (LPS-RS, 20 µg/10 µL) was administrated 30 min before LPS injection into the TG (10 µg/10 µL) or oral mucosa (10 µg/50 µL). In the postoperative pain model, rats were treated with LPS-RS (20 µg/10 µL) into the TG for three consecutive days after the incision. Facial heat and mechanical hyperalgesia were assessed hourly after LPS injection or intraoral incision. In addition, expression of NFκB was assessed in the TG on day 3 after intraoral incision. Our results showed that blockade of TLR4 in the TG attenuated facial heat and mechanical hyperalgesia induced by LPS or by mucosal incision, and that both conditions are associated to increase of phosphorylated NFκB in the TG. In conclusion, the present study suggests that activation of TLR4-NFκB signaling pathway in the TG contributes to the development of facial heat and mechanical hyperalgesia and may contribute to pain in inflammatory oral conditions.
Assuntos
Hiperalgesia , Receptor 4 Toll-Like , Gânglio Trigeminal , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate whether intraganglionic calcitonin gene-related peptide induced differential migraine-like responses in male and female rats. METHODS: Calcitonin gene-related peptide was injected in the trigeminal ganglion of male and female rats followed by assessment of periorbital mechanical allodynia with von Frey hairs. The influence of systemic treatment with sumatriptan or intraganglionic treatment with minocycline and propentofylline was determined on the calcitonin gene-related peptide-induced mechanical allodynia in male and female rats. One additional group was exposed to an aversive light 24 h after calcitonin gene-related peptide priming, followed by evaluation of periorbital mechanical threshold, and another group was tested in the elevated-plus maze. RESULTS: Intraganglionar calcitonin gene-related peptide-induced periorbital mechanical allodynia in female (0.5 to 6 h) and male rats (0.5 to 4 h). Systemic sumatriptan briefly attenuated the mechanical allodynia, but intraganglionar minocycline or propentofylline injection was effective only in male rats. Calcitonin gene-related peptide induced photic sensitivity in female and male rats (lasting 4 h and 1 h, respectively), as well as anxiety-like behavior. CONCLUSIONS: Intraganglionar calcitonin gene-related peptide may play a major role in migraine-like responses, including periorbital mechanical allodynia, light sensitivity and anxiety like-behavior. Female rats are likely to be more susceptible to calcitonin gene-related peptide effects and a better understanding of the sexual dimorphism in calcitonin gene-related peptide signaling may help to improve migraine therapy.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Hiperalgesia/metabolismo , Transtornos de Enxaqueca/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Feminino , Hiperalgesia/induzido quimicamente , Masculino , Transtornos de Enxaqueca/induzido quimicamente , Ratos , Ratos Wistar , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Caracteres Sexuais , Sumatriptana/farmacologia , Gânglio Trigeminal/efeitos dos fármacosRESUMO
The processing of grapes for the manufacture of juices and wines, generates large quantities of by-products rich in metabolites with antioxidant, antimicrobial, anti-inflammatory and cicatrizing activities. The high homology between human enzymes and snake venoms makes the latter valuable laboratory tools for the study of pathophysiological processes. Proteases and phospholipases A2 act in processes related to hemostasis and inflammatory response. Thus, in this work, dried pomace obtained from grape (Isabel, Niagara, Bordô, BRS Violeta and Blend cultivars) processing were evaluated on phospholipase, proteolytic, hemolytic and thrombolytic activities induced by snakes venoms and the content of phenolic compounds and minerals was evaluated. The dried pomace exerted inhibitory and potentiating actions in all analyzed activities. The enzymatic modulators present in the evaluated dried pomace have potential for therapeutic use, although their broad characterization is still necessary, in order to define adequate amounts and formulations to obtain efficacy and safety in their use.
Assuntos
Venenos de Serpentes/efeitos adversos , Vinho/classificação , Enzimas/análise , Compostos Fenólicos/análise , Fosfolipases A2/análise , Vitis/classificação , Resíduos Industriais/análiseRESUMO
Rats emit ultrasonic vocalizations (USVs) about 22 kHz and 50 kHz sound frequency to communicate the presence of negative or positive emotional states, respectively. The calling behavior may be influenced by several factors, including environmental factors. Likewise, pain behavior can be modulated according to the social context, and also can be transferred to conspecifics through direct observation and/or social interaction. Herein we investigated if acute pain induction was related to changes in emission of aversive and appetitive calls and how different social contexts affected the nociceptive behavior and USVs. Our results demonstrated that orofacial formalin injection in rats induced aversive calls in addition to the nociceptive behavior, and both are reduced by systemic treatment with morphine (2.5 mg/kg). Exposure of formalin-injected rats to cagemates had no effect on the nociceptive behavior or calls emitted by the demonstrator, but the observer showed emotional contagion of pain. In contrast, exposure of formalin-injected rats to non-cagemates decreased the nociceptive behavior of the demonstrator, without affecting the calls emission. The emotional contagion was not detected in non-cagemates or in cagemates separated by a visual barrier. In conclusion, we suggest that familiarity and the visual contact contributes to emotional contagion of pain. USV analysis may represent an additional measure in the evaluation of the emotional aspect of orofacial pain, and for the study of pain modulation.