• Vedran Deletis, Jay Shils, Juan Anso, Eduardo Villar Ortega, Laura Marchal-Crespo, Karin A Buetler, Andreas Raabe, and Kathleen Seidel.
• Albert Einstein College of Medicine, New York, NY, USA; Department of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia.
• Neuromodulation. 2023 Apr 1; 26 (3): 614619614-619.

ObjectiveThe mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve.Materials And MethodsThe ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-μV amplitude in ten sequential trials and "subthreshold" as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction.ResultsComparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz-10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%.ConclusionsHFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.

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