Histologic and physiologic evaluation of electrically stimulated peripheral nerve: Considerations for the selection of parameters

Helical electrodes were implanted around the left and right common peroneal nerves of cats. Three weeks after implantation one nerve was stimulated for 4–16 hours using charge-balanced, biphasic, constant current pulses. Compound action potentials (CAP) evoked by the stimulus were recorded from over the cauda equina before, during and after the stimulation. Light and electron microscopy evaluations were conducted at various times following the stimulation. The mere presence of the electrode invariably resulted in thickened epineurium and in some cases increased peripheral endoneurial connective tissue beneath the electrodes. Physiologic changes during stimulation included elevation of the electrical threshold of the large axons in the nerve. This was reversed within one week after stimulation at a frequency of 20 Hz, but often was not reversed following stimulation at 50–100 Hz. Continuous stimulation at 50 Hz for 8–16 hours at 400 μA or more resulted in neural damage characterized by endoneurial edema beginning within 48 hours after stimulation, and early axonal degeneration (EAD) of the large myelinated fibers, beginning by 1 week after stimulation. Neural damage due to electrical stimulation was decreased or abolished by reduction of the duration of stimulation, by stimulating at 20 Hz (vs. 50 Hz) or by use of an intermittent duty cycle. These results demonstrate that axons in peripheral nerves can be irreversely damaged by 8–16 hours of continuous stimulation at 50 Hz. However, the extent to which these axons may subsequently regenerate is uncertain. Therefore, protocols for functional electrical stimulation in human patients probably should be evaluated individually in animal studies.