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。最近的临床和临床前证据表明，迷走神经刺激（VNS）与触觉康复相结合，包括向不敏感的皮肤表面提供各种机械刺激，可以在正中神经和尺神经横断和修复后实现体感功能的实质性和持久恢复。在这里，我们测试了这样的假设：触觉康复的特定组成部分与迷走神经刺激相结合对于体感功能的恢复是必要的。在另一个单独队列的第二个实验中，我们研究了迷走神经刺激与触觉康复相结合是否可以提高熟练的前肢运动功能。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已预先注册 (https://osf.io/3tm8u/)。动物受到周围神经损伤（PNI），导致慢性感觉丧失。受伤八周后，对动物进行 VNS 植入，然后进行六周的触觉康复训练，其中包括对先前去神经的前爪重复应用两种不同的机械刺激之一（细丝或画笔）。与不使用 VNS 的触觉康复相比，VNS 结合细丝压痕或爪子刷牙可显着改善 PNI 后前肢缩回阈值的恢复。当 VNS 与刷牙配对时，效果大小是 VNS 与点压痕配对时的两倍。第二组中的独立复制证实，VNS 与刷子配对可将前肢缩回阈值恢复到正常。与未接受 VNS 的大鼠相比，这些大鼠在熟练的前肢任务中表现出显着改善。这些发现支持将 VNS 与触觉康复结合起来以改善神经损伤后体感和运动功能的恢复。此外，这项研究表明，与迷走神经刺激相结合的康复感觉特征决定了恢复程度。