The University of Texas at Dallas, Texas Biomedical Device Center, 800 West Campbell Road, Richardson, TX 75080-3021, United States; The University of Texas at Dallas, Erik Jonsson School of Engineering and Computer Science, Department of Bioengineering, 800 West Campbell Road, Richardson, TX 75080-3021, United States.
The University of Texas at Dallas, Texas Biomedical Device Center, 800 West Campbell Road, Richardson, TX 75080-3021, United States; The University of Texas at Dallas, School of Behavioral and Brain Sciences, 800 West Campbell Road, Richardson, TX 75080-3021, United States.
Behav Brain Res. 2021 Jan 1;396:112910. doi: 10.1016/j.bbr.2020.112910. Epub 2020 Sep 21.
Loss of sensory function is a common consequence of neurological injury. Recent clinical and preclinical evidence indicates vagus nerve stimulation (VNS) paired with tactile rehabilitation, consisting of delivery of a variety of mechanical stimuli to the hyposensitive skin surface, yields substantial and long-lasting recovery of somatosensory function after median and ulnar nerve transection and repair. Here, we tested the hypothesis that a specific component of the tactile rehabilitation paired with VNS is necessary for recovery of somatosensory function. In a second experiment in a separate cohort, we investigated whether VNS paired with tactile rehabilitation could improve skilled forelimb motor function. Elements of the study design, including planned sample size, assessments, and statistical comparisons, were preregistered prior to beginning data collection (https://osf.io/3tm8u/). Animals received a peripheral nerve injury (PNI) causing chronic sensory loss. Eight weeks after injury, animals were given a VNS implant followed by six weeks of tactile rehabilitation sessions consisting of repeated application of one of two distinct mechanical stimuli, a filament or a paintbrush, to the previously denervated forepaw. VNS paired with either filament indentation or brushing of the paw significantly improved recovery of forelimb withdrawal thresholds after PNI compared to tactile rehabilitation without VNS. The effect size was twice as large when VNS was paired with brushing compared to VNS paired with point indentation. An independent replication in a second cohort confirmed that VNS paired with brush restored forelimb withdrawal thresholds to normal. These rats displayed significant improvements in performance on a skilled forelimb task compared to rats that did not receive VNS. These findings support the utility of pairing VNS with tactile rehabilitation to improve recovery of somatosensory and motor function after neurological injury. Additionally, this study demonstrates that the sensory characteristics of the rehabilitation paired with VNS determine the degree of recovery.
感觉功能丧失是神经损伤的常见后果。最近的临床前和临床证据表明，迷走神经刺激 (VNS) 与触觉康复相结合，对感觉迟钝的皮肤表面施加各种机械刺激，可在正中神经和尺神经切断和修复后显著且持久地恢复躯体感觉功能。在这里，我们检验了这样一种假设，即与 VNS 结合的触觉康复的特定组成部分对于躯体感觉功能的恢复是必要的。在另一项单独队列的实验中，我们研究了 VNS 与触觉康复相结合是否可以改善熟练的前肢运动功能。该研究设计的要素，包括计划的样本量、评估和统计比较，在开始数据收集之前进行了预先登记（https://osf.io/3tm8u/）。动物接受了外周神经损伤 (PNI)，导致慢性感觉丧失。损伤后 8 周，动物接受 VNS 植入物，然后进行六周的触觉康复治疗，包括反复施加两种不同的机械刺激之一，即细丝或毛刷，到先前去神经支配的前脚。与 VNS 结合的细丝压痕或刷爪子明显改善了 PNI 后前肢撤回阈值的恢复，与没有 VNS 的触觉康复相比。与 VNS 结合的刷拭与 VNS 结合的点压相比，效果大小增加了一倍。在第二队列中的独立复制证实，VNS 与刷拭结合可将前肢撤回阈值恢复正常。与未接受 VNS 的大鼠相比，这些大鼠在熟练的前肢任务上的表现显著提高。这些发现支持将 VNS 与触觉康复相结合以改善神经损伤后躯体感觉和运动功能恢复的实用性。此外，这项研究表明，与 VNS 结合的康复的感觉特征决定了恢复的程度。
