Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE)
Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE)
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DOI：
10.1016/j.expneurol.2015.05.017
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发表时间：
2015-09-01
影响因子：
5.3
通讯作者：
Kerr, Bradley J.
中科院分区：
文献类型：
--
作者：
Benson, Curtis;Paylor, John W.;Kerr, Bradley J.
多发性硬化症（MS）的经典定义是运动缺陷，但它也与疼痛，抑郁和焦虑的继发症状有关。到目前为止，改变这些继发症状一直很困难。有证据表明，MS和动物模型实验性自身免疫性脑脊髓炎（EAE），通常用于研究疾病的病理生理学，可以通过运动调节。为了检查有限的自愿轮跑是否可以调节EAE疾病进展和疼痛的共病症状，允许患有EAE的小鼠每天接触跑轮1小时。每天只允许1小时的自愿运行导致了显着延迟疾病的临床症状的发作。使用Von Frey毛发评估机械性异常性疼痛的发展，并表明车轮运行对与EAE相关的疼痛超敏反应具有适度的积极影响。这些行为变化与脊髓背角中cFOS和磷酸化NR1阳性细胞数量减少有关。此外，在背角内，自愿轮跑减少浸润的CD3（+）T细胞的数量，并降低lba1免疫反应性的总体水平。使用高效液相色谱法（HPLC），我们观察到，车轮运行导致脊髓抗氧化剂谷胱甘肽水平的显着变化。氧化应激已分别显示有助于EAE疾病进展和神经性疼痛。这些结果共同表明，在患有EAE的小鼠中，自主运动活动可以延迟临床体征的发作并减少与疾病相关的疼痛症状。(C)2015 Elsevier Inc. All rights reserved.
Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1 h everyday. Allowing only 1 h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of lba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. (C) 2015 Elsevier Inc. All rights reserved.