• Evan R Rogers, Hans J Zander, and Scott F Lempka.
• Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan.
• J Pain. 2022 Mar 1; 23 (3): 434449434-449.

AbstractSpinal cord stimulation (SCS) is a popular neurostimulation therapy for severe chronic pain. To improve stimulation efficacy, multiple modes are now used clinically, including conventional, burst, and 10-kHz SCS. Clinical observations have produced speculation that these modes target different neural elements and/or work via distinct mechanisms of action. However, in humans, these hypotheses cannot be conclusively answered via experimental methods. Therefore, we utilized computational modeling to assess the response of primary afferents, interneurons, and projection neurons to conventional, burst, and 10-kHz SCS. We found that local cell thresholds were always higher than afferent thresholds, arguing against direct recruitment of these local cells. Furthermore, although we observed relative threshold differences between conventional, burst, and 10-kHz SCS, the recruitment order was the same. Finally, contrary to previous reports, axon collateralization produced complex changes in activation thresholds of primary afferents. These results motivate future work to contextualize clinical observations across SCS paradigms. PERSPECTIVE: This article presents the first computational modeling study to investigate neural recruitment during conventional, burst, and 10-kilohertz spinal cord stimulation for chronic pain within a single modeling framework. The results provide insight into these treatments' unknown mechanisms of action and offer context to interpreting clinical observations.Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

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