American Society for Peripheral Nerve

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Conditioning Electrical Stimulation is Superior to Postoperative Electrical Stimulation, Resulting in Enhanced Nerve Regeneration and Functional Recovery
Jenna-Lynn B Senger, MD1; K. Ming Chan, MD2; Ashley W Chan, (BSc)1; Jaret Olson, MD3; Michael J Morhart, MD, M.Sc3; Christine A Webber, PhD1
1University of Alberta, Edmonton, AB, Canada, 2Division of Physical Medicine & Rehabilitation, University of Alberta, Edmonton, AB, Canada, 3Division of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, AB, Canada

Background: The use of postoperative electrical stimulation (PES) to enhance peripheral nerve regeneration is currently the standard of care at many centers. Animal studies have confirmed that PES enhances staggered regeneration at the site of coaptation. However, unlike conditioning (preoperative) electrical stimulation (CES) it does not accelerate the rate of regeneration. Comparison of the regeneration and reinnervation outcomes of PES vs. CES is required to guide clinical management. This study tests the hypothesis that CES results in faster nerve regeneration and better functional outcomes compared to gold-standard PES.

Methods: Sprague Dawley rats were equally divided into four cohorts: i) CES alone, ii) PES alone, iii) CES + PES, and iv) sham (no ES). CES was delivered one week prior to nerve cut/coaptation, and PES was delivered immediately following coaptation. Length of nerve regeneration was assessed at 7 days post-coaptation (n=6/cohort), and physiological and behavioural testing were performed at 7 weeks post-coaptation (n=8/cohort).

Results: Animals treated with CES alone had significantly improved lengths of regeneration and sensorimotor reinnervation outcomes compared to all other cohorts. One-week post-injury, CES treated axons extended 8.5 + 0.6 mm, significantly longer than PES (3.6 + 0.3mm), CES + PES (5.5 + 0.5mm), or sham (2.7+ 0.3mm) (p<0.001). Compared to all other cohorts, sensory reinnervation was improved in the CES group, with significantly enhanced responsiveness to von Frey filament pressure sensitivity and increased intraepidermal nerve fiber reinnervation (p<0.001). Motor reinnervation was evaluated using behaviour (toe spread width, horizontal ladder test), electrophysiological (CMAP amplitude) and immunohistochemical (reinnervated neuromuscular junction) analysis, all of which were significantly improved in the CES cohort compared to all other groups (p<0.05).

Conclusion: CES significantly improves regeneration and reinnervation beyond that attainable with PES, which is the current clinical paradigm. To elucidate mechanistic insights, we are working to delineate molecular and cellular changes associated with each treatment modality. To establish its clinical utilities, efforts are currently underway to evaluate the effects of CES in patients with peripheral nerve injury.

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