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- ItemAcesso aberto (Open Access)Alterações encontradas no potencial visual evocado por padrão reverso em pacientes com esclerose múltipla definida(Conselho Brasileiro de Oftalmologia, 2007-12-01) Andrade, Eric Pinheiro De; Sacai, Paula Yuri [UNIFESP]; Berezovsky, Adriana [UNIFESP]; Salomão, Solange Rios [UNIFESP]; Universidade de Santo Amaro; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: Multiple sclerosis is an idiopathic demyelinating disease that may affect the optic nerve leading to acute unilateral visual loss, which could be observed by means of evoked visual potential (VEP). This exam is much valued for studying prechiasmatic visual paths in multiple sclerosis. PURPOSE: To analyze the findings of pattern reversal VEP in patients with prior diagnosis of multiple sclerosis and to compare them to visual acuity. METHODS: Twenty-four patients with a definite diagnosis of multiple sclerosis were submitted to pattern reversal VEP from October 2001 to March 2007. RESULTS: In P100 component response, at 15' and 1º stimuli, 19 eyes presented latency response up to 115 ms in both stimuli, which coincided in 6 eyes with latency response between 116 and 135 ms; 11 eyes had a latency response higher than 135 ms, and four eyes did not respond to stimuli. Correlating visual acuity with P100 latency for 15', in Pearson r correlation, r=0.85 with p=0.000000123, and for 1º, r = 0.87 with p=0.0000000338. CONCLUSION: Approximately 60.4% of patients presented abnormalities. However, the correlation between the P100 latency (15' and 1º) and visual acuity was statistically significant; therefore the better the visual acuity, the better the response to stimuli of the pattern-reversal VEP.
- ItemSomente MetadadadosAnálise de parâmetros inflamatórios e comportamentais em decorrência da indução da desmielinização química com cuprizona em ratos lewis expostos ao enriquecimento ambiental(Universidade Federal de São Paulo (UNIFESP), 2014-07-30) Serra-Oliveira, Nathalia [UNIFESP]; Castro, Glaucia Monteiro de [UNIFESP]; http://lattes.cnpq.br/2727707909050870; http://lattes.cnpq.br/2634685799181212; Universidade Federal de São Paulo (UNIFESP)The myelin in the central nervous system (CNS) is vulnerable to damage due to metabolic, toxic or autoimmune attacks change. In this way, neurological damage such as demyelination causes motor, sensory, and behavioral changes. Multiple sclerosis is one of the most prevalent demyelinating disorders resulting from an aberrant immune response directed against oligodendrocytes. One of the biggest challenges is to find strategies that improve the remyelination process, although it occurs, is usually incomplete or failed. In this context, cuprizone has been used as animal model of demyelination, sharing some characteristics of multiple sclerosis. It is known that sensory, motor, cognitive and social stimulus modulate the CNS throughout life and the exposure to enriched environment (EE) provides new sensorimotor experiences, enhancing integration of CNS and promoting neuroplasticity. We hypothesize that the clinical signs of demyelination induced by cuprizone can be minimized by daily exposure to EE. In behavioral tests, it was found that the cuprizone group showed impairment in motor coordination in sensitivity and exploratory behavioral, similar to signs of anxiety. On the other hand, the EE minimized or reversed behavioral changes resulting from cuprizone. In demyelinated lesion, the density of oligodendrocytes is reduced, the astrocytic and microglial activation are increased in the corpus callosum compared with the control group, however the EE reduced the damage caused to oligodendrocytes by cuprizone. The TNF-? induces apoptosis of oligodendrocytes, accentuating demyelination. It was found that the concentrations of this cytokine significantly increased when compared to the cuprizone EE and control groups. Our results suggest that the EE can minimize the impact of white mater lesions enabling improved clinical signs and behavioral changes caused by demyelination exerting neuroprotective action.
- ItemAcesso aberto (Open Access)Análise do efeito da terapia com laser de baixa intensidade na reversão da desmielinização crônica induzida pela Cuprizona(Universidade Federal de São Paulo, 2022-01-28) Araujo, Lucas Colombo [UNIFESP]; Castro, Glaucia Monteiro de [UNIFESP]; http://lattes.cnpq.br/2727707909050870; http://lattes.cnpq.br/3662515800871316; Universidade Federal de São Paulo (UNIFESP)A esclerose múltipla é uma doença crônica, de caráter autoimune e que se caracteriza pela inflamação do sistema nervoso central, levando à degeneração da bainha de mielina que envolve os axônios e ocasionando a diminuição da capacidade de transmissão do impulso nervoso entre neurônios. A falta de terapias eficazes no tratamento desta doença impulsiona a busca por novos tratamentos. Neste trabalho utilizamos fotobiomodulação terapêutica, já bastante conhecida na área da fisioterapia no tratamento de inflamações e utilizada nesse estudo para a remielinização causada experimentalmente pela cuprizona, com a hipótese de que os animais terão o quadro de desmielinização causado pela cuprizona revertido. O presente trabalho tem o objetivo de demonstrar o efeito do tratamento com a fotobiomodulação em camundongos tratados com cuprizona. Foram utilizados 20 camundongos C57Bl/6, machos, com 6 semanas de idade, distribuídos nos grupos (n=5): Controle (CT), Controle Laser (CTL), Cuprizona (CPZ) e Cuprizona Laser (CPZL). A desmielinização foi induzida pela adição de 0,2% de cuprizona à dieta moída durante 7 semanas para os grupos CPZ e CPZL. O tratamento com a fotobiomodulação foi aplicado de maneira transcranial nos grupos CTL e CPZL nas últimas três semanas de tratamento com a cuprizona. Foi realizado o teste Rotarod no começo e no final do experimento para avaliação do desempenho motor dos animais. Para avaliação do processo de desmielinização, foi feita a análise da densidade de mielina em corpo caloso pela coloração do Luxol Fast Blue. Nossos resultados mostram que não houve diferença estatística no teste motor dos animais, apesar de ter havido uma quantidade de quedas mais acentuada no grupo cuprizona, porém tivemos resultados significativos nas diferenças de densidade de mielina dentro dos grupos e no peso dos animais ao final do experimento, o que nos dá indícios de que o tratamento com o laser pode ter um papel importante na diminuição desses sintomas.
- ItemAcesso aberto (Open Access)Avaliação dos distúrbios do movimento em pacientes com doenças desmielinizantes(Universidade Federal de São Paulo (UNIFESP), 2017-11-30) Silva, Carolina Candeias da [UNIFESP]; Borges, Vanderci [UNIFESP]; Oliveira, Enedina Maria Lobato de [UNIFESP]; http://lattes.cnpq.br/9619603975043505; http://lattes.cnpq.br/2742450111759824; http://lattes.cnpq.br/8841277346692168; Universidade Federal de São Paulo (UNIFESP)Objective: To describe the prevalence and characteristics of movement disorders in patients with MS (multiple sclerosis) and NMOSD (neuromyelitis optica spectrum disorder) followed at the Neuroimmunology clinic at Universidade Federal de São Paulo. In addition, to investigate the association between MS, NMOSD, disability, movement disorders and quality of life. Methods: A cross-sectional study of patients with demyelinating diseases was conducted from June 2015 to September 2016. Patients aged 18 years or older, without significant cognitive impairment and with diagnostic criteria for MS or NMOSD were eligible. We evaluated 268 patients, 15 were excluded. The main exclusion criteria was other possible cause related with the movement disorder. Patients were evaluated with interview and physical exam by a neurologist specialist in movement disorder. We used the following tools: the EDSS (Expanded Disability Status Scale), the Fahn Tolosa and Marín tremor rating scale, the modified Ashworth scale, for assessment of spasticity, and EuroQoL- 5 Dimensions questionnaire, for analysis of quality of life. Results: From 253 patients included, 26% presented with movement disorders. The majority of the patients was female (74.3%), with a mean age of 40.36 years (SD = 11.74). The median EDSS score of included patients was 2.5 with interquartile range of 1.0- 6.0. Paroxysmal dystonia (n=32) was the most common movement disorder, followed by tremor (n=27). The prevalence of tremor in MS was 12.5% and intention tremor was the most common (82%). Patients with MS and low EDSS score (<4,0), compared to NMOSD, have fewer movement disorders. Paroxysmal dystonia was strongly associated to NMOSD diagnosis (OR=22.07, 95%CI=2.56 - 189.78; p=0.005). The mean of utility scores of quality of life was 0.58 (SD=0.26), patients with MS have 0.15 points higher on average than patients with NMOSD, and patients with movement disorders have 0.083 points lower than those without them. Conclusion: The presence of movement disorders in patients with demyelinating diseases seems to be related with severity and progression of the disease. Paroxysmal dystonia is significantly more associated with NMOSD, and may be a clinical marker of this. Intention tremor was the most common movement disorder in MS. It has been demonstrated an impact on the quality of life of patients with demyelinating diseases and movement disorders.
- ItemSomente MetadadadosCuprizone demyelination induces a unique inflammatory response in the subventricular zone(Biomed Central Ltd, 2016) Hillis, James M.; Davies, Julie; Mundim, Mayara Vieira [UNIFESP]; Al-Dalahmah, Osama; Szele, Francis G.Background: Cuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation. Methods: We studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay. Results: Cuprizone caused loss of myelin basic protein (MBP) immunofluorescence in the CC suggesting demyelination. Cuprizone increased the density of CD45+/Iba1+ microglial cells and also increased Gal-3 expression in the CC. Surprisingly, the number of Gal-3+ and CD45+ cells decreased in the SVZ after cuprizone, suggesting inflammation was selectively reduced therein. Inflammation can regulate SVZ proliferation and indeed the number of phosphohistone H3+ (PHi3+) cells decreased in the SVZ but increased in the CC in both genotypes after cuprizone treatment. BrdU+ SVZ cell numbers also decreased in the SVZ after cuprizone, and this effect was significantly greater at 3 weeks in Gal-3(-/-) mice compared to WT, suggesting Gal-3 normally limits SVZ cell emigration following cuprizone treatment. Conclusions: This study reveals a uniquely regulated inflammatory response in the SVZ and shows that Gal-3 participates in remyelination in the cuprizone model. This contrasts with more severe models of demyelination which induce SVZ inflammation and suggests the extent of demyelination affects the SVZ neurogenic response.
- ItemAcesso aberto (Open Access)Derivados do ácido fumárico utilizados no tratamento de esclerose múltipla: um overview(Universidade Federal de São Paulo, 2021-12-15) Esteves, Arthur Caputo [UNIFESP]; Veiga, Thiago André Moura [UNIFESP]; http://lattes.cnpq.br/8190975614526360Produtos naturais são substâncias resultantes do metabolismo secundário dos seres vivos. Diferentemente dos metabolitos primários, são particulares de espécies ou gêneros específicos. Plantas, fungos, bactérias e organismos marinhos são as principais fontes de produtos naturais de interesse humano, pois muitas vezes apresentam atividade biológica interessante, representando importantes precursores para candidatos a fármacos. Muitos produtos naturais passam por derivatizações químicas, realizadas sinteticamente ou até por engenharia genética, para a melhoria de suas atividades biológicas, resultando em fármacos mais potentes e especializados, presentes no tratamento de doenças como câncer, diabetes, glaucoma, entre outras. Recentemente, derivados do ácido fumárico tem ganhado destaque no tratamento de esclerose múltipla, sendo que três deles foram aprovados pela Food and Drug Administration (FDA), agência federal norteamericana: monometil fumarato, fumarato de diroximel e siponimode fumarato, os quais são conhecidos comercialmente como Bafiertan®, VumerityTM e Mayzent®, respectivamente. Neste contexto, esse projeto buscou realizar um levantamento bibliográfico sobre esses fumaratos dentro do período de 2010 a 2021, levando em conta as metodologias de obtenção dessas espécies químicas, mecanismos de ação e resultados clínicos relacionados ao tratamento da esclerose múltipla. Por fim, buscase também investigar a capacidade que esses fármacos tem para tratar outras doenças além da esclerose múltipla, mostrando a versatilidade dessas moléculas.
- ItemAcesso aberto (Open Access)Diabetes insípido em paciente com esclerose múltipla(Sociedade Brasileira de Endocrinologia e Metabologia, 2008-02-01) Weiler, Fernanda G. [UNIFESP]; Blumberg, Kátia [UNIFESP]; Liboni, Claudia S. [UNIFESP]; Roque, Eduardo A. C. [UNIFESP]; Góis, Aécio Flávio Teixeira de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Multiple Sclerosis (ME) is a chronic progressive disease characterized by relapses of demyelination that can occur anywhere in the brain stem, spinal cord and optic nerve. Since central diabetes insipidus (DI) is mainly caused by central nervous system damage (such as trauma, surgery, tumor, infection, sarcoidosis), ME is included among its possible etiologies. However, this association is not commonly described. The clinical suspicion must be made in the presence of polyuria and polydipsia or refractory hypernatremia (in patients without free access to water) during the evolution of ME. We will describe a clinical report in which this association occurred and, after the beginning of desmopressin therapy, the clinical findings were reverted.
- ItemSomente MetadadadosDifferent MOG(35-55) concentrations induce distinguishable inflammation through early regulatory response by IL-10 and TGF-beta in mice CNS despite unchanged clinical course(Elsevier B.V., 2015-02-01) Dias, Alyria Teixeira; Ribeiro De Castro, Sandra Bertelli; De Souza Alves, Caio Cesar; Mesquita, Felipe Pereira; Visona De Figueiredo, Nathalia Stela; Evangelista, Marcilene Gomes; Marques Nogueira Castanon, Maria Christina; Juliano, Maria Aparecida [UNIFESP]; Ferreira, Ana Paula; Univ Fed Juiz de Fora; Fed Univ Valleys Jequitinhonha & Mucuri; Universidade Federal de São Paulo (UNIFESP)Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by different protocols, which show distinct cytokine and antibody production. the factors involved in this heterogeneity remain unclear. the relevance of MUG concentration in triggering a regulatory response in the chronic model of EAE is imprecise. the aim of this study was investigate if 100 or 300 mu g of MOG(35-55) could induce different EAE profiles. Modifications in the concentration of MUG were able to change the patterns of chemokines, cytokines, percentage of cells, inflammatory infiltrate and the development of a regulatory response. However, these changes were unable to modify the intensity of response, which explains the chronic progression of the disease in both concentrations. the results presented in this study contribute to understanding the intricate mechanisms that trigger EAE and provide insights into the pathogenesis of various forms of MS. (C) 2015 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Distúrbio do sono em pacientes com esclerose múltipla : a relação entre fadiga e sonolência excessiva diurna(Universidade Federal de São Paulo (UNIFESP), 2017-08-31) Braga, Douglas Martins [UNIFESP]; Oliveira, Enedina Maria Lobato de [UNIFESP]; Prado, Gilmar Fernandes do [UNIFESP]; http://lattes.cnpq.br/2617510083171521; http://lattes.cnpq.br/9619603975043505; http://lattes.cnpq.br/8910992825218125; Universidade Federal de São Paulo (UNIFESP)Sleep disorders in patients with multiple sclerosis have various causes and interfere with daytime wakefulness. Objective: This study assessed the correlation between fatigue, excessive daytime sleepiness and level of disability. Method: Retrospective review of medical records from patients with multiple sclerosis to collect data on severity of fatigue, disability, daytime sleepiness, and depression. From 912 medical records reviewed, 122 reported daytime sleepiness: 67% had relapsing remitting, 12% had primary progressive, and 21% had secondary progressive. Results: In 95% of the patients with relapsing remitting who complained of daytime sleepiness and fatigue, association was found between these symptoms and neurological disability. Patients with relapsing remitting who complained of daytime sleepiness and fatigue also experienced depression (p = 0.001). No association between fatigue, excessive daytime sleepiness, depression, and disability was found in patients with progressive disease. Conclusion: In relapsing remitting, there is correlation between functional disability, excessive daytime sleepiness and fatigue, a finding not confirmed in primary progressive and secondary progressive form.
- ItemAcesso aberto (Open Access)Doenças desmielinizantes recorrentes na população pediátrica: estudo retrospectivo dos pacientes acompanhados no ambulatório de doenças desmielinizantes da Universidade Federal de São Paulo - Escola Paulista de Medicina(Universidade Federal de São Paulo (UNIFESP), 2018-04-26) Fragomeni, Manuela de Oliveira [UNIFESP]; Oliveira, Enedina Maria Lobato de [UNIFESP]; http://lattes.cnpq.br/9619603975043505; http://lattes.cnpq.br/5590230320617326; Universidade Federal de São Paulo (UNIFESP)Introdução: Esclerose múltipla (EM) e neuromielite óptica (NMO) são doenças inflamatórias desmielinizantes do sistema nervoso central (SNC), que ocorrem com maior frequência em adultos jovens, sendo raros os casos com início na população pediátrica, abaixo de 18 anos de idade. São doenças de etiologia autoimune com fisiopatologia, quadro clínico, tratamento e prognósticos distintos. Na faixa etária pediátrica, muitas vezes estas condições apresentam sintomas clínicos semelhantes e pode haver dificuldade em distingui-las entre si e entre outros diagnósticos diferenciais. Objetivos: Descrever as características clínicas e epidemiológicas, avaliar a resposta ao tratamento e comparar as principais características clínicas dos pacientes com EM e NMO pediátricas acompanhados na Universidade Federal de São Paulo (UNIFESP). Métodos: Estudo retrospectivo dos pacientes acompanhados por EM e NMO com início antes dos 18 anos na UNIFESP. Foram selecionados para análise aqueles que preenchessem os critérios diagnósticos de McDonald 2010 para EM e os critérios de 2006 para NMO. Para análise de tratamento, foram selecionados os pacientes com acompanhamento superior a 6 meses. Resultados: Sessenta e oito pacientes preencheram os critérios de inclusão para EM e foram selecionados para análise. A idade média de início de sintomas foi de 15 anos, 73,5% dos pacientes eram do sexo feminino e a média de tempo de acompanhamento foi de 6,7 anos. A taxa anualizada de surtos (TAS) média foi de 0,82 surto/ano e o índice de progressão (IP) médio foi de 0,31 ponto EDSS/ano. O tratamento com betainterferona (b-IFN) e acetato de glatiramer (AG) foi seguro, com redução estatisticamente significativa do IP com uso de b-IFN de alta dose e AG. Onze pacientes preencheram os critérios de inclusão para NMO: a idade média de início de sintomas foi de 14 anos, 72,7% dos pacientes eram do sexo feminino e a média de tempo de acompanhamento foi de 6,3 anos. A TAS média foi de 1,5 surto/ano e o IP médio foi de 2,2 ponto EDSS/ano. O tratamento com azatioprina foi seguro, com redução estatisticamente significativa do IP. Pacientes com NMO atingiram EDSS 6 significativamente mais cedo do que os pacientes com EM. Conclusões: As características clínicas dos pacientes com EM e NMO pediátricas avaliadas são semelhantes às descritas previamente. Os tratamentos oferecidos são seguros e efetivos nesta população. NMO é uma doença mais agressiva e incapacitante do que a EM na população pediátrica.
- ItemSomente MetadadadosEfeitos do laser de baixa intensidade na desmielinização induzida por cuprizona em camundongos(Universidade Federal de São Paulo (UNIFESP), 2016-03-24) Duarte, Katherine Chuere Nunes [UNIFESP]; Castro, Glaucia Monteiro de [UNIFESP]; http://lattes.cnpq.br/2727707909050870; http://lattes.cnpq.br/0526412538364715; Universidade Federal de São Paulo (UNIFESP)Multiple sclerosis is an autoimmune, inflammatory, and demyelinating disease of the central nervous system (CNS). The inflammation, mediated by immunological attacks against myelin, leads to demyelination and, subsequently, neuron loss. The lack of an efficient therapy as treatment of demyelination has motivated the investigation of new therapeutic approaches. Studies show that laser therapy is efficient in promoting neurogenesis and modulation of inflammation in rodents? CNS. The aim of this study was to evaluate the effects of low-level laser therapy (LLLT) on cuprizone induced demyelination. We used C57BL/6 mice, randomly distributed in Control Laser, Cuprizone, and Cuprizone Laser groups. Demyelination was induced by feeding the animals with a diet including 0.2% cuprizone for four weeks. The LLLT were applied in Control Laser and Cuprizone Laser mice for three consecutive days, in the third and fourth weeks of the experiment. Motor coordination was assessed by the rotarod test. Twenty-four hours after the final laser session, the animals were euthanized to collect blood and brains. Histological analyses were carried out by immunohistochemistry and Luxol Fast Blue staining (LFB). The results showed that laser-treated animals demonstrated better motor performance. In the nervous tissue, the LLLT treatment attenuated the demyelination indicated by LFB staining and immunolabeling. Laser therapy increased the number of oligodendrocytes precursor cells (OPCs), modulated microglial and astrocytes activation, and reduced toxicity induced by cuprizone. These results suggest that low-level laser therapy was effective in motor recovery, attenuation of demyelination, modulation of inflammation, proliferation of OPCs, and toxicity control
- ItemAcesso aberto (Open Access)Neurite óptica recorrente : estudo retrospectivo descritivo e comparativo dos pacientes acompanhados no Setor de Neuroimunologia, da Disciplina de Neurologia, da Universidade Federal de São Paulo, de acordo com diagnóstico final de neuropatia óptica recorrente crônica, doenças do espectro da neuromielite óptica e esclerose múltipla(Universidade Federal de São Paulo (UNIFESP), 2017) Gonçalves, Alessandra Billi Falcão [UNIFESP]; Oliveira, Enedina Maria Lobato de [UNIFESP]; http://lattes.cnpq.br/9619603975043505; http://lattes.cnpq.br/6836332477371321; Universidade Federal de São Paulo (UNIFESP)Objetivos: Descrever e comparar as caracteristicas dos pacientes com NO recorrente como sintoma inicial, de acordo com o diagnóstico final: Esclerose Múltipla (EM), Doenças do espectro da Neuromielite Óptica (NMOSD) ou neuropatia óptica inflamatória recorrente crônica (CRION). Métodos: Estudo retrospectivo incluindo pacientes com NO recorrente inicial do banco de dados, contendo 1823 prontuários, do setor de Neuroimunologia da Universidade Federal de São Paulo. Estes pacientes foram classificados de acordo com seu diagnóstico final em dezembro de 2016 em EM, NMOSD ou CRION e então as características clínicas, laboratoriais e achados de ressonância magnética de cada grupo foram descritas e comparadas entre si. Resultados: 33 pacientes com neurite óptica recorrente unilateral ou bilateral foram incluídos: 6 com diagnóstico final de EM, 14 com NMOSD e 13 com CRION. A maioria dos pacientes era do sexo feminino, com neurite óptica unilateral e severa no primeiro episódio. A acuidade visual no pior olho foi igual ou pior a 20/200 em 61,5% dos pacientes com CRION, 85,7% nos pacientes com NMOSD e 16,7% dos pacientes com EM. O sistema funcional visual (SFV) inicial foi maior ou igual a 5 em, respectivamente, 63,6%, 85,7% e 16,7% destes grupos. Sete pacientes soropositivos (77,8%) e três soronegativos (25,0%) apresentaram mielite transversa durante o seguimento. Conclusões: Soropositividade para anti-AQP-4, achados de RM e sistema funcional visual inicial são fatores preditivos para o diagnóstico final. NO na EM é menos grave e sua recorrência, incomum em comparação com os outros grupos. Pacientes com NMOSD e CRION comportam-se de forma semelhante mas NMOSD tende a apresentar pior acuidade visual.
- ItemSomente MetadadadosThe role of kinin B-1 and B-2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: Evidence for the involvement of astrocytes(Elsevier B.V., 2013-06-01) Dutra, Rafael C.; Bento, Allisson F.; Leite, Daniela F. P.; Manjavachi, Marianne N.; Marcon, Rodrigo; Bicca, Maira Assuncao; Pesquero, Joao B. [UNIFESP]; Calixto, Joao B.; Universidade Federal de Santa Catarina (UFSC); Universidade Federal de São Paulo (UNIFESP)Multiple sclerosis (MS) is a progressive, demyelinating inflammatory disease of the human central nervous system (CNS). While the primary symptoms of MS affect motor function, it is now recognized that chronic pain is a relevant symptom that affects both animals and MS patients. There is evidence that glial cells, such as astrocytes, play an important role in the development and maintenance of chronic pain. Kinins, notably bradykinin (BK) acting through B-1 (B1R) and B-2 (B2R) receptors, play a central role in pain and inflammatory processes. However, it remains unclear whether kinin receptors are involved in neuropathic pain in MS. Here we investigated by genetic and pharmacological approaches the role of kinin receptors in neuropathic pain behaviors induced in the experimental autoimmune encephalomyelitis (EAE) mouse model. Our results showed that gene deletion or antagonism of kinin receptors, especially B1R, significantly inhibited both tactile and thermal hypersensitivity in EAE animals. By contrast, animals with EAE and treated with a B1R selective agonist displayed a significant increase in tactile hypersensitivity. We also observed a marked increase in B1R mRNA and protein level in the mouse spinal cord 14 days after EAE immunization. Blockade of B1R significantly suppressed the levels of mRNAs for IL-17, IFN-gamma, IL-6, CXCL-1/KC, COX-2 and NOS2, as well as glial activation in the spinal cord. of note, the selective B-1 antagonist DALBK consistently prevented IFN-induced up-regulation of TNF-alpha and IL-6 release in astrocyte culture. Finally, both B1R and B2R antagonists significantly inhibited COX-2 and NOS2 expression in primary astrocyte culture. the B1R was co-localized with immunomarker of astrocytes in the spinal cord of EAE-treated animals. the above data constitute convincing experimental evidence indicating that both kinin receptors, especially the B-1 subtype, exert a critical role in the establishment of persistent hypersensitivity observed in the EAE model, an action that seems to involve a central inflammatory process, possibly acting on astrocytes. Thus, B-1 selective antagonists or drugs that reduce kinin release may have the potential to treat neuropathic pain in patients suffering from MS. (C) 2013 Elsevier Inc. All rights reserved.