Application of electrical stimulation for peripheral nerve regeneration: Stimulation parameters and future horizons

Peripheral nerve trauma impacts both social and occupational quality of life. Patients are typically young and subsequently suffer from lifelong disability. Unlike the central nervous system, the peripheral nervous system has the capacity to regenerate along previous or new connections. Yet, complete functional recovery has been an elusive clinical objective despite the development of advanced microsurgical techniques to repair nerves. In recent decades significant amount of work has expanded the focus towards establishing new facets of adjuvant treatment to improve nerve regeneration. One potential therapy is the application of electric stimulation of peripheral nerves immediately following microsurgical repair. Mounting pre-clinical and clinical evidence demonstrated the efficacy of electrical stimulation in improving nerve regeneration and functional recovery. In this paper, we review the potential therapeutic benefits of electrical stimulation and the current limitations of regeneration after nerve injury. We also summarize the proposed mechanisms of electrical stimulation in increasing the regenerative capacity of peripheral nerves, including evidence from human clinical trials. Finally, we discuss stimulation parameters and safety profiles with an eye towards future treatment strategies. Combining electrical stimulation with conductive scaffolds has the potential to improve successful nerve regeneration and may have profound clinical implications to nerve injury patients.