Enhancing Radial Nerve Regeneration: The Impact of Brief Electrical Stimulation on Functional Reinnervation in a Non-Human Primate Model

Introduction: Brief electrical stimulation (BES) has been shown to accelerate axon outgrowth across nerve injuries. However, prior studies have been limited to small animal models, making the potential translation of these findings to humans less clear. To address this gap, we conducted an analysis in a non-human primate model to evaluate the impact on hand reinnervation and resulting function following radial nerve transection and repair.

Methods: Four rhesus macaques underwent one hour of biphasic BES (20 Hz, 0.2 ms pulses, at 2x motor threshold) applied to the radial nerve of one arm using hook electrodes (the experimental arm). In contrast, sham stimulation (no current) was administered to the contralateral nerve (the control arm).

One week following BES, bilateral radial nerve transection and repair was performed. Weekly functional assessments, along with bimonthly neurophysiological evaluations including Compound Muscle Action Potential (CMAP) and Motor Unit Number Estimation (MUNE) were conducted for a duration of six months post-surgery.

Results: All repaired nerves demonstrated recovery, with a notable trend toward faster and more substantial functional outcomes in the experimental arms. Three primates exhibited accelerated motor recovery in the experimental arm, with improved wrist extension and metacarpophalangeal joint extension at earlier stages. Electrophysiological analysis indicated earlier and more robust reinnervation, with higher CMAP and MUNE values in experimental arms of three primates at six months. Post-op histological analysis of the fourth primate showed a large neuroma in the experimental arm, explaining the lack of similar augmented recovery.

Conclusion : Our findings suggest that brief electrical stimulation prior to surgical intervention facilitates faster motor recovery and enhances nerve regeneration in non-human primate models following radial nerve injury. This approach offers a promising strategy for optimizing functional recovery in clinical settings before nerve surgery.