In Vivo Measurements Reveal that Both Low- and High-frequency Spinal Cord Stimulation Heterogeneously Modulate Superficial Dorsal Horn Neurons

• Published in: Neuroscience 2023-06, Vol.520, p.119-131
• Main Authors: Kuo, Su-Wei, Zhang, Tianhe, Esteller, Rosana, Grill, Warren M.
• Format: Article
• Language: English
• Subjects: Animals; C-fiber; Male; Neurons - physiology; pain; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; single unit recording; Spinal Cord - physiology; Spinal Cord Dorsal Horn; spinal cord stimulation; Spinal Cord Stimulation - methods
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2023.04.010

•Spinal cord stimulation modulates excitability of superficial dorsal horn neurons.•Changes in excitability dependent on intensity and duration of stimulation.•Excitability of neurons with spontaneous activity was facilitated.•Excitability of other neuron types was reduced. Current sub-perception spinal cord stimulation (SCS) is characterized by the use of high-frequency pulses to achieve paresthesia-free analgesic effects. High-frequency SCS demonstrates distinctive properties from paresthesia-based SCS, such as a longer time course to response, implying the existence of alternative mechanism(s) of action beyond gate control theory. We quantified the responses to SCS of single neurons within the superficial dorsal horn (SDH), a structure in close proximity to SCS electrodes, to investigate the mechanisms underlying high-frequency SCS in 62 urethane-anesthetized male rats. Sciatic nerve stimulation was delivered to isolate lumbar SDH neurons with evoked C-fiber activity. The evoked C-fiber activity before and after the application of SCS was compared to quantify the effects of SCS across stimulation intensity and stimulation duration at three different stimulation frequencies. We observed heterogeneous responses of SDH neurons which depended primarily on the type of unit. Low-threshold units with spontaneous activity, putatively inhibitory interneurons, tended to be facilitated by SCS while the other unit types were suppressed. The effects of SCS were more prominent with increased stimulation duration from 30 s to 30 m across frequencies. Our results highlight the importance of inhibitory interneurons in modulating local circuits of the SDH and the importance of local circuit contributions to the analgesic mechanisms of SCS.