The Role of Ionic Currents in Peripheral Nerve Regeneration

Various factors may result in peripheral nerve injury leading to permanent functional loss. Here, we review the role of calcium and potassium ions in peripheral nerve regeneration and repair. This narrative review of the literature collected its data by searching Google Scholar, PubMed, Elsevier, Springer, Wiley, EBSCO, Scopus, and Science Direct. Publications were searched with no particular time restriction from 1997 to 2021, including all types of study. About 100 relevant papers were found from 1997, 77 of which were selected for this study. Both beta subunits of sodium channels are expressed in peripheral neurons, and drugs that affect those channels may facilitate nerve repair. Riluzole is a sodium/glutamate antagonist which has recently entered clinical trials for spinal cord injury. Riluzole's neuroprotective effects are due to sodium channel blockade and, subsequently, the prevention of Ca2+ overflow. Besides, 4-aminopyridine (4-AP) is a neurotransmitter of potassium channel blockers that increases the rate of functional improvement following peripheral nerve damage by promoting remyelination. Verapamil is a calcium channel blocker that stimulates an endogenous anti-inflammatory response and reduces pro-inflammatory processes, thus causing pain modulation. Inhibition of ROCKs accelerate the regeneration and functional restoration after spinal-cord damage in mammals, and inhibition of the Rho/ROCK pathway has been additionally proven efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer’s disease, and neuropathic ache. Therefore, the neurite outgrowth of surviving neurons is necessary for nerve regeneration to reinnervate target tissue after nerve damage. One of the critical components of the damage response process is a local translation in axons, and it is critical for the regenerative outcome. On the other hand, it provides new axonal regrowth molecules and induces signals returning to the cell's soma to partake in regenerative pathways and survival.