Dorsal horn dendrite polarization during Spinal Cord Stimulation (SCS) predicted using the quasi-uniform-mirror assumption.

While the mechanisms of Spinal Cord Stimulation are traditionally assumed to follow pacing of dorsal columns axons, the development of sub-paresthesia SCS and new waveforms has encouraged consideration of different cellular targets. Given their relative proximity to the stimulation electrodes and role in pain processing (e.g., synaptic processing and gate control theory), spinal cord dorsal horn interneurons may be direct targets of stimulation. We developed a novel computational modeling pipeline termed 'quasi-uniform-mirror assumption' and apply it to predict polarization of dorsal horn inter-neuron cell types (Islet type, Central type, Stellate/Radial, Vertical-like) to SCS. The quasi-uniform-mirror assumption allows prediction, for each cell type and location in the dorsal horn, the peak and axis of dendritic polarization as well as the impact of stimulation pulse width. For long pulse (dc), the peak polarization per mA of SCS with a bipolar montage were: Islet type 3.5 mV, Central type 2 mV, Stellate/Radial 1.4 mV, Vertical-like 2.5 mV. For Stellate/Radial the peak dendritic polarization was dorsal-ventral, and for Islet type Central peak dendrite polarization was in the rostral-caudal axis. For Islet type and Central type cells peak dendrite polarization was between stimulation electrodes, while for Stellate/Radial and Vertical-like peak dendrite polarization was under stimulation electrodes. The impact of pulse width depended on cell membrane time constants, which in the quasi-uniform-mirror assumption are uniform first-order. Assuming 1 ms time constant, for a 1 ms or 100 us pulse width, the peak dendrite polarization decreases (from the dc values) by ~33% and ~88%. These results suggest, for the conditions modeled, maximum polarization is of islet-cells in the superficial dorsal horn at locations between electrodes; applying 2 mA 1 ms pulse SCS, the peak islet-cell dendrite polarization is ~4.7 mV. Polarizations of a few mV have been shown to modulate synaptic processing through sub-threshold mechanisms. ### Competing Interest Statement MR is the President of the International Neuromodulation Society and Director at Large of the Neuromodulation Society of Australia and New Zealand. MR discloses research activities (paid to research institution) for Boston Scientific, Mainstay Medical, Medtronic, Nevro, Presidio Medical and Saluda Medical, historical equity interest in Stimwave, Lungpacer and SPR Therapeutics, and stock options in Saluda Medical and Presidio Medical. The City University of New York holds patents on brain stimulation with MB as inventor. MB has equity in Soterix Medical Inc. MB consults, received grants, assigned inventions, and/or served on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biovisics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple, Ybrain, Ceragem, Remz. MB is supported by grants from Harold Shames and the National Institutes of Health: NIH-NIDA UG3DA048502, NIH-NIGMS T34 GM137858, NIH-NINDS R01 NS112996, NIH-NINDS R01 NS101362, and NIH-G-RISE T32GM136499.