Simultaneous 10 kHz and 40 Hz spinal cord stimulation increases dorsal horn inhibitory interneuron activity

Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Low-intensity, paresthesia-free, 10 kHz SCS has demonstrated statistically- and clinically-superior long-term pain relief compared to conventional SCS. 10 kHz SCS has been proposed to operate via selective activation of inhibitory interneurons in the superficial dorsal horn. In contrast, 40 Hz SCS is presumed to operate largely via dorsal column fiber activation. To determine if these mechanisms may be implemented synergistically, we examined the effect of each type of stimulation both independently and simultaneously on putatively inhibitory and putatively excitatory neurons in the superficial dorsal horn. When 10 kHz SCS was applied relatively caudally to the measured spinal segment, simultaneous with 40 Hz SCS applied relatively rostrally to that spinal segment, inhibitory interneurons demonstrated a median increase of 26 spikes/s compared to their baseline firing rates. Median firing rate increases of inhibitory interneurons were 8.7 and 5.1 spikes/s during 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally, respectively. By comparison, the median firing rate of excitatory interneurons increased by 4.1 spikes/s during simultaneous 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally. Median firing rate increases of excitatory interneurons were 13 and 0.8 spikes/s during 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally, respectively. This suggests that simultaneously applying 10 kHz SCS caudally and 40 Hz SCS rostrally may provide greater pain relief than either type of SCS alone by increasing the firing rates of inhibitory interneurons, albeit with greater excitatory interneuron activation.