O modelo de dor inflamatória induzida pela carragenina como estratégia para avaliar a ação de drogas sobre a dor miofascial

A dor miofascial orofacial vem sendo tratada com analgésicos, anti-inflamatórios, relaxantes musculares, fisioterapia, laserterapia e placas oclusais. Contudo, muitas vezes, tais condutas falham em amenizar o quadro doloroso, havendo a necessidade de testar outras estratégias de tratamento. Metodologia: Uma opção para avaliação experimental dessas terapias seria o teste de dor induzido pela carragenina, associado ao teste de avaliação do limiar nociceptivo, originalmente desenvolvido para avaliar a ação de drogas nas patas de roedores. Sendo assim, o presente estudo analisou a nocicepção causada pela carragenina em masseteres de ratos, através do teste de Von Frey, correlacionando-a com alterações teciduais produzidas por esta droga. A carragenina foi injetada no músculo masseter de ratos, enquanto o grupo controle recebeu soro fisiológico. O limiar nociceptivo foi mensurado com um analgesímetro digital antes da administração da carragenina e 5 horas, 1, 3 e 7 dias após o seu uso. Decorridos 8 dias da intervenção, os animais foram eutanasiados, sendo seus masseteres encaminhados para processamento histológico e coloração H&E. Resultados: Observou-se uma diminuição do limiar da resposta nociceptiva em todos os períodos no grupo com carragenina, quando comparado com o grupo controle, havendo diferença significante nas 5 horas. A análise histológica do grupo experimental mostrou a presença de espaços perimisial e endomisial alargados e preenchidos por uma matriz com alguns linfócitos, muitos macrófagos e raros mastócitos. Conclusão: Os resultados indicaram que a associação de uma droga inflamatória com o método Von Frey pode ser uma opção para o estudo do efeito de terapias de dor miofascial

Descrição dos achados linguísticos e neurológicos de gemelares nascidos pré-termo aos dois anos de idade

Introduction: Prematurity, low birth weight and multiple births are risk factors for structural changes in the brain, as well as deviations in motor, cognitive, social and language development. Objective: To describe language findings and investigate the presence of neurological changes in preterm twins born at two years of age. Method: This is a cross-sectional study based on data analysis of the medical records of six pairs of low birth weight preterm twins, of both sexes, at two years of age, attended to at the State Center for the Prevention and Rehabilitation of Persons withDisabilities - CEPRED, in Salvador-Bahia-Brazil. To this end, information regarding birth was collected; the clinical history; the imaging exams; and the speech, neurological and interdisciplinary assessments. Results: preterm twins had atypical language development and neurological changes that may compromise oral language development. From the neurological point of view, abnormalities common to the premature newborn, such as peri-intraventricular hemorrhage, were observed. Conclusion: Multiple births associated with prematurity and low birth weight may pose risks to the childs language acquisition.Introdução: A prematuridade, o baixo peso ao nascer e os nascimentos múltiplos são fatores de risco para alterações estruturais no cérebro, assim como para desvios no desenvolvimento motor, cognitivo, social e de linguagem. Objetivo: Descrever os achados linguísticos e investigar a presença de alterações neurológicas em gemelares nascidos pré-termo, aos dois anos de idade. Método: Trata-se de um estudo do tipo corte transversal, realizado por meio da análise de dados dos prontuários de seis pares de gêmeos nascidos pré-termo, com baixo peso ao nascer, de ambos os sexos, aos dois anos de idade, atendidos no Centro Estadual de Prevenção e Reabilitação da Pessoa com Deficiência – CEPRED, em Salvador-Bahia-Brasil. Para tanto, foram coletadas as informações referentes ao nascimento; a história clínica; os exames de imagem; e as avaliações fonoaudiológica, neurológica e interdisciplinar. Resultados: Os gemelares nascidos pré-termo apresentaram desenvolvimento linguístico atípico e alterações neurológicas que podem comprometer o desenvolvimento da linguagem oral. Do ponto de vista neurológico, foram observadas anormalidades comuns ao recém-nascido prematuro, como a hemorragia peri-intraventricular. Conclusão: Os nascimentos múltiplos associados à prematuridade e ao baixo peso ao nascer podem oferecer riscos à aquisição da linguagem da criança

Estudo do veneno de Tityus serrulatus (Scorpiones; Buthidae) procedente do estado da Bahia, Brasil

The scorpion Tityus serrulatus is known as the most important species according to the medical point of view, because it is what causes the most serious registered accidents for the Brazilian country. This work deals with the characterization of the poison of scorpion T. serrulatus in different regions of Bahia/Brazil, through the attainment of the DL50 of the poison the determination of pulmonary edema induced for the poison and the characterization of the neurotoxic effects induced by the poison. The poison was obtained through electric stimulation using itself of a extractor (method of Brazil, 1949), developed specifically for this end. Male Swiss mice (18-22g) had been used to evaluate the toxicity for the method of Finney (1971). The pulmonary induction of edema was calculated by the difference of weight of the controlled and tested lung. The obtained DL50 was of 93.6 µg mouse. We can attribute this high value to low toxicity of the poison for the animals of the studied region (Metropolitan Region of Salvador). The observed toxicity was of 3 to 7 times lower than that the poison of the same species in other regions of Brazil (São Paulo and Minas Gerais). Our results in the performed experiments to study acute lung edema had demonstrated that the poison of T. serrulatus of the State of the Bahia does not induce death.O escorpião Tityus serrulatus é conhecido como a espécie mais importante, do ponto de vista médico, pois é o que causa os acidentes mais graves registrados (para) no território brasileiro. Este trabalho trata da caracterização do veneno de escorpiões T. serrulatus, procedentes de diferentes regiões da Bahia-Brasil, através da obtenção da DL50, a observação da existência do edema pulmonar e caracterização dos distúrbios neurológicos induzido pela peçonha. O veneno foi obtido através de estímulo elétrico, utilizando-se de um extrator desenvolvido especificamente para esse fim. Camundongos Swiss machos (18-22g) foram utilizados para avaliar a toxicidade pelo método de Finney (1971). A indução de edema pulmonar foi calculada pela diferença de peso úmido dos pulmões controle e teste. A DL50 obtida foi de 96,3 µg/ camundongo, considerada alta, demonstrando a baixa toxicidade do veneno. A toxicidade observada foi de 3 a 7 vezes menor que a do veneno da mesma espécie em outras regiões do Brasil (São Paulo e Minas Gerais). Nossos resultados demonstraram que o veneno de T. serrulatus do Estado da Bahia não induz o edema pulmonar agudo, tanto na avaliação do índice peso pulmonar/peso corporal quanto na avaliação morfológica. Esses fatores podem explicar a ausência de óbitos nos acidentes por Tityus serrulatus na Região Metropolitana do Salvador (RMS) e é concordante com dados de outros autores que, no período de 1982-2000, não registraram óbito nos acidentes escorpiônicos na mesma região

Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom.

Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells.Intraplantar injection of MLV (1-10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema.In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms

Participation of mast cells (MCs) in paw edema induced by <i>Micrurus lemniscatus</i> venom.

<p>(A) Groups of rats were treated with compound 48/80 (0.1 to 5.0 mg/mL i.p. twice a day for 5 consecutive days) or an equal volume of vehicle i.p. (control) before MLV injection (5 μg/paw). Edema was evaluated using a plethysmometer at the time points shown. Data are expressed as % increase in paw volume compared with the control paw. (B) Degranulation of mesenteric mast cells was assessed 15 min after venom injection by counting the percentage of cells with extruded granules in the histological preparation. (C, D) Toluidine blue staining of mesenteric mast cells treated with apyrogenic saline (C) or MLV (2.8 μg/g) (D). The mesentery had minimal mast cell degranulation after i.p. injection with apyrogenic saline and extensive mast cell degranulation after injection with MLV. Values are the mean ± SEM of five animals. * <i>p</i> < 0.05 compared with control group.</p

Effect of biogenic amine-receptor antagonists on paw edema induced by <i>Micrurus lemniscatus</i> venom.

<p>Groups of animals were treated with promethazine (5 mg/kg, i.p.) (an H₁ receptor antagonist), thioperamide (5 mg/kg, i.p.) (an H₃R/H₄R receptor antagonist) or methysergide (5 mg/kg, i.p.) (a nonselective 5-HT receptor antagonist) 30 min before intraplantar injection of MLV (5 μg/paw). The increase in volume of each paw (edema) was measured using a plethysmometer. Data were calculated as the difference between both paws and are expressed as a % increase in paw volume. Values are the mean ± SEM of five animals. * <i>p</i> < 0.05 compared with control group.</p

Participation of mast cells (MCs) in paw edema induced by <i>Micrurus lemniscatus</i> venom.

<p>(A) Groups of rats were treated with compound 48/80 (0.1 to 5.0 mg/mL i.p. twice a day for 5 consecutive days) or an equal volume of vehicle i.p. (control) before MLV injection (5 μg/paw). Edema was evaluated using a plethysmometer at the time points shown. Data are expressed as % increase in paw volume compared with the control paw. (B) Degranulation of mesenteric mast cells was assessed 15 min after venom injection by counting the percentage of cells with extruded granules in the histological preparation. (C, D) Toluidine blue staining of mesenteric mast cells treated with apyrogenic saline (C) or MLV (2.8 μg/g) (D). The mesentery had minimal mast cell degranulation after i.p. injection with apyrogenic saline and extensive mast cell degranulation after injection with MLV. Values are the mean ± SEM of five animals. * <i>p</i> < 0.05 compared with control group.</p

Effect of bradykinin BK₂-receptor antagonist (HOE 140) on paw edema induced by <i>Micrurus lemniscatus</i> venom.

<p>Groups of animals were treated with HOE 140 (5 μg/paw) concomitantly with MLV (5 μg/paw, i.pl.). The increase in volume of each paw (edema) was measured using a plethysmometer. Results were calculated as the difference between hind paws and are expressed as a % increase in paw volume. Values are the mean ± SEM of five animals. None of the results were statistically significant.</p

Time course of rat paw edema induced by selected doses of <i>Micrurus lemniscatus</i> venom.

<p>Increased paw volume was determined at various time points after intraplantar injection of MLV (1–10 μg/paw) into one paw and apyrogenic saline into the contralateral paw (control paw). The increase in volume of each paw (edema) was measured using a plethysmometer. Differences between paws were expressed as a % increase in paw volume. Values are the mean ± SEM of five animals. * <i>p</i> < 0.05 compared with MLV (1 μg/paw).</p

Effect of capsaicin and tachykinin NK₁- and NK₂-receptor antagonists (SR14033 and SR 48968, respectively) on edema induced by <i>Micrurus lemniscatus</i> venom.

<p>Groups of animals were treated with capsaicin (15, 30 and 50 mg/kg, s.c.) for 4 consecutive days to deplete substance P from sensitive primary afferent neurons or NK₁- or NK₂ receptor antagonists. Both SR 140333 (1 nmol/paw) and SR 48968 (10 nmol/paw) were co-injected i.pl. with MLV (5 μg/paw). The increase in volume of each paw (edema) was measured using a plethysmometer. Results were calculated as the difference between hind paws and are expressed as a % increase in paw volume. Values are the mean ± SEM of five animals. * p < 0.05 compared with control group.</p