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Trigeminal and Peripheral Electrical Stimulation to Augment Peripheral Nerve Regeneration in a Rodent Forelimb Gap Repair Model
Peter Nicksic, MD1; D'Andrea T Donnelly, BA2; Weifeng Zeng, MD3; Aaron J Suminski, PhD4; Poore O. Samuel, MD, PhD5; Aaron M. Dingle, PhD6
1University of Wisconsin Madison, Madison, WI; 2University of Wisconsin, Madison, WI; 3University of Wisconsin - Madison, Division of Plastic and Reconstructive Surgery, Madison, WI; 4University of Wisconsin, Madison, Madison, WI; 5Division of Plastic & Reconstructive Surgery, University of Wisconsin, Madison, Madison, WI; 6Plastic and Reconstructive Surgery, University of Wisconsin - Madison, Madison, WI

Introduction: Peripheral nerve injuries are a common problem that incur significant morbidity and loss of function to patients. One method to improve outcomes in nerve regeneration is electrical stimulation (ES), which has been shown to improve axonal growth when administered peripherally and evoke targeted neuroplasticity at the level of the cortex when administered to cranial nerves. While previous literature has shown that vagus nerve stimulation improves outcomes of peripheral nerve injury, stimulating the vagus nerve is invasive in that it requires surgical implantation of a nerve cuff. By contrast, the trigeminal nerve is a superficial somatosensory nerve that can be stimulated transcutaneously in humans. The aim of this study is to demonstrate that the trigeminal nerve can be used as a novel target for ES to improve functional outcomes of peripheral nerve injury in a rat forelimb model.
Materials and Methods: After being trained to proficiency in a reach and grasp task, 46 male Lewis rats were randomized into 4 groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with intraoperative peripheral ES, and (4) nerve injury with trigeminal ES during post injury rehabilitation. Nerve injuries consisted of complete transection of the median and ulnar nerve 1cm proximal to the medial epicondyle of the humerus with a 2mm gap repair. Following repair of the nerve injury, rats in intraoperative peripheral ES group were fitted with a bipolar cuff electrode proximal to the repair and stimulated for 1 hour. At week 5 of recovery, all rats were implanted with a bipolar cuff electrode on the supraorbital branch of the trigeminal nerve. During rehabilitation, the trigeminal ES group received 500ms of stimulation immediately following each successful reach and grasp. Median peak pull force, task success rates, and paw withdrawal thresholds were collected both preinjury and throughout rehabilitation.
Results: Pre-injury baseline median peak pull force and paw withdrawal thresholds were 155.5g and 18.46g, respectively. We are currently collecting data on the post-injury functional rehabilitation component of the protocol.
Conclusions: The trigeminal nerve offers a promising target for ES as it can be stimulated transcutaneously in humans and does not require surgical implant of a nerve cuff. We anticipate that the effect of trigeminal stimulation will be like that of the vagus nerve, which has been demonstrated to evoke targeted neuroplasticity and improve functional outcomes in animal models.


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