Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st-12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th-9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-γ-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

O desempenho da dupla tarefa na Doença de Parkinson / The dual task performance in Parkinson's disease

INTRODUÇÃO: A capacidade de o indivíduo realizar duas tarefas ao mesmo tempo é um pré-requisito para uma vida normal. Em circunstâncias normais, a realização concomitante de tarefas motoras e cognitivas é comum. OBJETIVO: O objetivo deste estudo foi analisar o desempenho de pacientes com Doença de Parkinson na realização de dupla tarefa motora-cognitiva. MÉTODO: Dois grupos foram estudados. Um grupo foi composto por 10 indivíduos saudáveis e o outro por 10 pacientes com diagnóstico de Doença de Parkinson, ambos com idades entre 47 e 75 anos, pareados em relação ao gênero e idade. Foi solicitado que vestissem uma camisa de botões o mais rapidamente possível de forma isolada (tarefa simples) e enquanto verbalizavam nomes próprios femininos (dupla tarefa), em ordem aleatória. Cada tarefa foi repetida três vezes. O tempo de movimento e os erros cometidos foram analisados. RESULTADOS: Os pacientes levaram mais tempo para completar ambas as tarefas (p= 0,006) quando comparados aos indivíduos saudáveis. Ambos os grupos cometeram mais erros na dupla tarefa (p= 0,03). Houve uma redução no tempo de movimento com a repetição da tarefa (p= 0,039). CONCLUSÕES: Estes resultados sugerem que indivíduos com Doença de Parkinson apresentam um prejuízo no desempenho motor em relação ao grupo controle, no entanto, o custo para o desempenho desta tarefa independe da interferência motora-cogntiva e a possibilidade de melhora do desempenho com a prática é real.

INTRODUCTION: A capacity to perform two tasks at the same time is a prerequisite for an individual to have a normal life. Under normal circumstances, performing motor and cognitive tasks concomitantly is common. OBJECTIVE: The aim of this study was investigate the motor-cognitive dual task performance in Parkinson's disease patients. METHOD: Two groups were studied. One group was composed by 10 healthy individuals and the other by 10 patients with a diagnosis of Parkinson's disease. In both groups, the ages were between 47 and 75 years and the individuals were paired in relation to gender and age. They were asked to put on a button-up shirt as fast as possible as a single task and also while saying girls' names in random order (dual task). Each task was repeated three times. The movement time and errors committed were analyzed. RESULTS: The patients took more time to complete both tasks (p= 0.006) in relation to the healthy group. Both groups committed more errors in the dual task (p= 0.03). There was a reduction in the movement time with the repetition of the task (p= 0.039) for both groups. CONCLUSION: These results suggest that individuals with Parkinson's disease present a loss in motor performance in relation to healthy individuals. However, the cost of performing the task is independent of motor-cognitive interference and the possibility of performance's improvement with practice is real.