Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice

Abstract

Background:Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes.Methods:C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the sciatic nerve was transected and repaired, and, in the latter 2 groups, ES was applied after repair. Postoperatively, changes to gene expression from dorsal root ganglia were measured after 24 hours. The number of motoneurons regenerating axons was determined by retrograde labeling at 7 days. Histomorphological analyses of the nerve were performed at 14 days. Function was evaluated serially with use of behavioral tests up to 56 days postoperatively, and relative muscle weight was evaluated.Results:Compared with the no-ES group, both ES groups demonstrated increased regeneration-associated gene expression within dorsal root ganglia. The 10-minute and 60-minute ES groups demonstrated accelerated axon regeneration compared with the no-ES group based on increased numbers of labeled motoneurons regenerating axons (mean difference, 202.0 [95% confidence interval (CI), 17.5 to 386.5] and 219.4 [95% CI, 34.9 to 403.9], respectively) and myelinated axon counts (mean difference, 559.3 [95% CI, 241.1 to 877.5] and 339.4 [95% CI, 21.2 to 657.6], respectively). The 10-minute and 60-minute ES groups had improved behavioral recovery, including on grid-walking analysis, compared with the no-ES group (mean difference, 11.9% [95% CI, 3.8% to 20.0%] and 10.9% [95% CI, 2.9% to 19.0%], respectively). There was no difference between the ES groups in measured outcomes.Conclusions:A 10-minute ES protocol accelerated axon regeneration and facilitated functional recovery.Clinical Relevance:The brief (10-minute) ES protocol provided similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair mice model and merits further studies.

Complete Foot Drop With Normal Electrodiagnostic Studies

“…With the tourniquet then released, we used a nerve stimulator to stimulate the common peroneal nerve for 15 minutes before closure. [24][25][26]…”

The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury

“…Short-duration ES protocols (i.e., 10 min) would improve clinical translation and limit peri-operative complexity. Mouse models have demonstrated no significant difference between one-hour of ES and 10 min of ES (16 Hz, 100 μsec) in transection and repair groups based on histomorphological analysis, gait analysis, and mechanical and cold sensitivity [ 88 ]. Both ES groups, however, demonstrated accelerated axonal regeneration compared to control based on labeled regenerating motoneuron axons, myelinated axon counts, and walking track analysis [ 88 ].…”

“…Mouse models have demonstrated no significant difference between one-hour of ES and 10 min of ES (16 Hz, 100 μsec) in transection and repair groups based on histomorphological analysis, gait analysis, and mechanical and cold sensitivity [ 88 ]. Both ES groups, however, demonstrated accelerated axonal regeneration compared to control based on labeled regenerating motoneuron axons, myelinated axon counts, and walking track analysis [ 88 ]. Roh et al further corroborated these findings, showing that 10 min of ES is sufficient to elicit similar therapeutic effects to one-hour of ES in transection and repair murine models [ 64 ].…”

“…Building on promising pre-clinical evidence [ 64 , 88 ], a multi-center, double-blind RCT from Moore et al is evaluating patient outcomes following a 10 min ES protocol [ 114 ]. In this study, patients undergoing cubital tunnel decompression surgery are randomized to receive 10 min of 20 Hz ES intraoperatively or no stimulation.…”

Traumatic peripheral nerve injuries: diagnosis and management

“…However, there may be a role for this approach after muscle reinnervation has occurred to increase muscle strength as an adjunct to sensory re-education. Low-frequency repetitive nerve stimulation is a more promising technique and has been shown to stimulate rapid motor reinnervation postoperatively [76–78,79 ▪ ,80,81 ▪ ]. Optimization of stimulation settings and evaluation of this technique in specific clinical scenarios is still required [76,82].…”