(20) Characterizing Therapeutic Window and Carry-Over Effects of High Frequency Electrical Nerve Block in Rodent Model.

Introduction: Pathological peripheral nerve activity is a hallmark of multiple diseases such as muscle spasms, spasticity, tics and choreas resulting in significant disruptions to quality of life. Arresting undesired action potentials could help mitigate sensory and motor symptoms. Kilohertz high frequency alternating current (KHFAC) can block nerves within seconds with conduction returning to the nerve fibers recover within a few seconds of turning block off.. It is necessary to assess the long-term safety of Kilohertz high frequency alternating current and determine the therapeutic window to achieve the desired clinical effects.

Methods: The sciatic nerve was exposed in an acute in-vivo rat model. Three bipolar platinum electrodes were implanted on the sciatic nerve (two stimulation electrodes being proximal (PS) and distal (DS) to a central block electrode). Stimulation was applied using the AM-Systems stimulator at a suprathreshold amplitude at 1Hz while recording the peak measured force from the gastrocnemius muscle. The PS/DS muscle force ratio of force was monitored. The block was applied using the Nerve Excitation Control Through Alternating Current (AC) Regulation (NECTAR) development unit (NIH HORNET Cleveland Open-Source Modular Implant Innovators Community (COSMIIC) funding), controlled by LabVIEW software at block threshold, suprathreshold and subthreshold amplitudes at 10 KHz and 20 KHz frequency.

Results: Preliminary analyses show that with application of KHFAC for durations of up to 20 minutes, rapid complete recovery of nerve conduction occurs. Prolonged application of KHFAC 30 minutes and beyond show a carry over block effect (COBE) which can take hours to recover completely. Prolonged application can also result in lasting effects on the nerve conduction system seen by decrease in stimulation force. Suprathreshold and subthreshold KHFAC block amplitudes were also evaluated; these experiments revealed that suprathreshold KHFAC block amplitudes show a greater amount of COBE however the application of subthreshold KHFAC shows little to no carryover effect even with extended periods of application.

Conclusion: These experiments have shown that application of amplitudes above the block threshold of KHFAC increases the carry over block effect duration. Cumulative Block applied over more than 30 minutes at block threshold and suprathreshold also gives a prolonged carry over block effect. However, supra and sub threshold application using subthreshold values could be used to safely deliver KHFAC over extended period while mitigating onset response and carry over block effect. The prolonged block effect and histological changes that might occur with extended application of KHFAC are also being tested in a chronic animal model.