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活动依赖性治疗对外周神经损伤后轴突再生和神经病理性疼痛的差异影响。

Differential effects of activity dependent treatments on axonal regeneration and neuropathic pain after peripheral nerve injury.

机构信息

Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.

出版信息

Exp Neurol. 2013 Feb;240:157-67. doi: 10.1016/j.expneurol.2012.11.023. Epub 2012 Nov 30.

DOI:10.1016/j.expneurol.2012.11.023
PMID:23201096
Abstract

Activity treatments are useful strategies to increase axonal regeneration and functional recovery after nerve lesions. They are thought to benefit neuropathy by enhancing neurotrophic factor expression. Nevertheless the effects on sensory function are still unclear. Since neurotrophic factors also play a fundamental role in peripheral and central sensitization, we studied the effects of acute electrical stimulation and early treadmill exercise on nerve regeneration and on neuropathic pain, and the relation with the expression of neurotrophins. After sciatic nerve section and suture repair, rats were subjected to electrical stimulation (ES) for 4h after injury, forced treadmill running (TR) for 5 days, or both treatments combined. Sciatic nerve section induced hyperalgesia in the medial area of the plantar skin in the injured paw. TR and ES differently but positively reduced adjacent neuropathic pain before and after sciatic reinnervation. ES enhanced motor and sensory reinnervation, and combination with TR induced strong agonistic effects in relieving pain. The differential effects of these activity treatments were related to changes in neurotrophic factor mRNA levels in sensory and motor neurons. ES speeded up expression of BDNF and GDNF in DRG, and of BDNF and NT3 in the ventral horn. TR reduced the levels of pro-nociceptive factors such as BDNF, NGF and GDNF in DRG. Combination of ES and TR induced intermediate levels suggesting an optimal balancing of treatment effects.

摘要

活动治疗是增加轴突再生和神经损伤后功能恢复的有用策略。它们被认为通过增强神经营养因子的表达有益于神经病变。然而,其对感觉功能的影响仍不清楚。由于神经营养因子在外周和中枢敏化中也起着至关重要的作用,我们研究了急性电刺激和早期跑步机运动对神经再生和神经病理性疼痛的影响,以及与神经营养因子表达的关系。在坐骨神经切断和缝合修复后,大鼠在损伤后接受 4 小时的电刺激(ES)、5 天的强制跑步机运动(TR)或两种治疗方法的联合治疗。坐骨神经切断在受伤爪子的足底皮肤内侧区域引起痛觉过敏。TR 和 ES 不同但积极地减轻了坐骨神经再支配前后相邻的神经病理性疼痛。ES 增强了运动和感觉神经再支配,与 TR 联合使用可产生强烈的缓解疼痛作用。这些活动治疗的差异作用与感觉和运动神经元中神经营养因子 mRNA 水平的变化有关。ES 加速了 DRG 中 BDNF 和 GDNF 的表达,以及腹角中 BDNF 和 NT3 的表达。TR 降低了 DRG 中促伤害因子如 BDNF、NGF 和 GDNF 的水平。ES 和 TR 的联合诱导出中间水平,提示治疗效果达到最佳平衡。

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