Acute Nerve Pedicle Transfer after Transection Prevents Neuroma Formation and Demonstrates Potential for Reinnervation in a Rat Sciatic Nerve Injury Model

Purpose: Residual limb pain is a debilitating condition affecting 20-30% of amputees. The presence of symptomatic neuromas appreciably increases the risk of developing residual limb pain. Nerve pedicle transfer (NPT), comprising both targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), seek to provide a "target" for transected nerves with the goal of preventing neuroma formation. The current study aims to identify mechanistic drivers of axonal changes after NPT in a validated rodent traumatic nerve injury model. Methods: Our study utilized a preclinical model of traumatic nerve injury, where the sciatic nerve was transected sharply to generate neuromas. Our treatment groups included control (no repair), targeted muscle reinnervation (TMR, sensory branch coapted proximally to motor branch to biceps femoris) and regenerative peripheral nerve interface (RPNI, sensory branch connected to free ipsilateral EDL muscle graft). Our primary endpoint, neuroma formation, was assessed by histology and diffusion tensor MR imaging (DTI). Functional reinnervation was further assessed by electromyography of the biceps femoris and free EDL graft. Results: At the histologic level, acute NPT improved collagen organization at the nerve coaptation interface compared to controls. DTI imaging further characterized significant fractional anisotropy with disorganized axonal regeneration in controls, whereas NPTs had in-plane fibers without evidence of neuroma. Using EMG, both regenerative peripheral nerve interfaces and targeted muscle reinnervation groups demonstrated active twitch stimulus in distal targets, suggestive of functional reinnervation. Conclusions: Taken together, our data demonstrate physiologic changes at the nerve coaptation interface that support healthy, organized axonal regeneration in prevention of neuroma formation. Future directions of the project include defining fiber tractography changes across the time-course of nerve regeneration to establish a probabilistic model of nerve recovery to distinguish successful and unsuccessful repairs.