Table 3.

Studies documenting MoA of 10 kHz SCS.

Study (First Author et al., Year of Publication)	Type (In Vitro, Ex Vivo, In Vivo or Clinical)	Model	Key Finding
Lee et al., 2020 [91]	In vivo and ex vivo	In vivo and ex vivo electrophysiological approaches: In vivo experiments: adult male Sprague Dawley rats Ex vivo experiments: Transgenic mice expressing green fluorescent protein in GABAergic neurons	10 kHz SCS may inhibit pain sensory processing in the spinal dorsal horn by uniquely activating inhibitory interneurons without activating dorsal column fibers, resulting in paresthesia-free pain relief.
Liao et al., 2020 [93]	In vivo, sham controlled	Spared nerve injury Sprague-Dawley rats	10 kHz SCS applied to the T10/T11 spinal cord significantly attenuated spared nerve injury-induced mechanical hyperalgesia compared with the sham stimulation group. Western blotting revealed a significant attenuation of ERK1, ERK2, JNK1, and p38 activation in the dorsal root ganglia and the spinal dorsal horn.
Liao et al., 2020 [94]	In vivo, sham controlled	Spared nerve injury Sprague-Dawley rats	10 kHz SCS treatment attenuated spared nerve injury -induced neuropathic pain and partially restored the altered glutamate uptake after spared nerve injury.
DeGroote et al., 2020 [95]	Clinical, Prospective study	Patients with FBSS treated with 10 kHz SCS; resting state functional magnetic resonance imaging (rsfMRI)	Increased strength in functional connectivity between the left dorsolateral prefrontal cortex and the right anterior insula significantly correlated with the minimum clinically important difference value of the Pittsburgh sleep quality index.
DeGroote et al., 2020 [96]	Clinical, prospective	Patients with FBSS treated with 10 kHz SCS; neuroimaging MRI (Voxel-Based Morphometry Diffeomorphic Anatomical Registration Through Exponentiated Lie)	10 kHz SCS influences structural brain regions over time. The volume of the hippocampus decreased bilaterally after three months with a positive correlation with back pain intensity.
Telkes et al., 2020 [97]	Clinical, prospective	Patients with FBSS treated with 10 kHz SCS; electroencephalogram (EEG)	Stronger relative alpha power in the somatosensory region. Shift in peak frequency from theta to alpha Rhythms compared to baseline. Changes in ODI scores positively correlated with alpha/theta peak power ratio in frontal and somatosensory regions.