Molecular Basis of Surgical Coaptation Techniques in Peripheral Nerve Injuries

Abstract

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon’s decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

End-to-Side Neurorrhaphy Technique: Exploring Neuronal Regeneration to Restore Nerve Function

“…Additionally, macrophage-assisted elimination of myelin debris, production of growth-promoting factors, along with stimulation of extracellular matrix remodeling, enhance the nerve regeneration process [2].…”

“…Peripheral nerve injuries affect 2-2.8% of polytrauma patients, being associated with impairment of the functioning of the upper and lower extremities [1]. The occurrence of a complex process is crucial for the neuronal regeneration of the damaged nerve [2].…”

“…Initially, nerve membranes are stimulated to undergo a sealing process, due to the action of calpain, which is activated by the prompt influx of calcium and sodium. In this first moment, the proximal nerve stump is stimulated by action potentials, triggering the activation of the second messenger cAMP, which consequently releases pro-regenerative transcription factors [2].…”

“…Despite these two phases, it is also necessary to eradicate the axons and myelin present in the distal stumps, as debris produce inhibitory signals, impeding axonal neural development from the proximal stump. The Wallerian degeneration (WD) is vital for this process [2].…”

Management of Superficial and Deep Peroneal Nerve Neuromas with Targeted Muscle Reinnervation in Nonamputees: Operative Technique and Early Outcomes

“…The property of being tension-free is crucial to a successful coaptation as it allows for faster axonal sprouting and final growth into motor nerve endplates. 11 In cases of doubt, alternating dorsiflexion and plantar flexion of the foot can help with visualization of muscle displacement and whether coaptation is adequate to ensure tension-free coaptation.…”