Award: William H. Sweet Young Investigator Award

Authors: Alexander B. Dru, MD; Lauren Dewberry, BS; Kevin Otto, PhD; Kyle Allen, PhD; Daniel Hoh, MD (Gainesville, FL)

Introduction:

Pain management for chronic sciatica often results in long-term opioid use leading to dependence, dosage increases, and diminished benefit. Our group previously discovered kilohertz (kHz) frequency modulation (50kHz/3Volts) of the sciatic nerve (SN) eliminates tactile allodynic responses in a validated rat model of sciatic neuropathy, with visual preservation of motor function. Here, we inspect and quantify the selective slow fiber (<5m/s) inhibition observed with the 50kHz/3V modulation.

Methods:

A Lewis rat was placed under general anesthesia and right SN exposed. A dual-electrode stimulator cuff was implanted on the proximal SN, recording cuff around the tibial nerve distally (1.9 cm separation), and SN neuromodulator between the cuffs. Compound action potentials (CAPs) were elicited with charge-balanced 500µA/0.1ms biphasic pulses. Frequency-voltage combinations (30-100 kHz in 5 kHz increments at 3, 5, 7,and 9 V peak-to-peak) were applied to the SN during CAP induction. Each trial consisted of 5 CAPs before, 20 CAPs during, and 10 CAPs after neuromodulation. CAPs were recorded on an amplitude-time graph with integrals of peaks corresponding to specific fiber activation.

Results:

The integral of the <5m/s combined peak before and during 50kHz/3V modulation was 0.048 and 0.016, respectively, representing 67.0% slow fiber inactivation with preservation of muscle stimulus artifact indicating unblocked motor neurons. The integrals of the 4.7 m/s (slow Aδ fiber) and 1.3 m/s (c fiber) peaks before/during modulation were 0.023/0.007 and 0.025/0.009, representing 69.6% and 64.0% inactivation, respectively.

Conclusion:

Sciatic neuromodulation at kilohertz frequency produces rapidly reversible sensory nerve block in a rat model of peripheral neuropathy. Our experiment provides an electrophysiological explanation for the selective muting of downstream-source allodynic discomfort and upstream neuropathy with respect to the neuromodulator location observed in our initial sciatica rat study. This offers additional proof of concept for a pulse generator-sciatic system for durable treatment of painful neuropathy in humans.