Frequency-Dependent Neural Modulation of Dorsal Horn Neurons by Kilohertz Spinal Cord Stimulation in Rats

Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In this study, using a novel preparation, we investigated the impact of varying kilohertz frequency SCS on dorsal horn neuron activation. Employing calcium imaging on isolated spinal cord slices, we found that extracellular electric fields at kilohertz frequencies (1, 3, 5, 8, and 10 kHz) induce distinct patterns of activation in dorsal horn neurons. Notably, as the frequency of extracellular electric fields increased, there was a clear and significant monotonic escalation in neuronal activity. This phenomenon was observed not only in superficial dorsal horn neurons, but also in those located deeper within the dorsal horn. Our study demonstrates the unique patterns of dorsal horn neuron activation in response to varying kilohertz frequencies of extracellular electric fields, and we contribute to a deeper understanding of how kHF-SCS induces paresthesia-free pain relief. Furthermore, our study highlights the potential for kHF-SCS to modulate sensory information processing within spinal pain circuits. These insights pave the way for future research aimed at optimizing kHF-SCS parameters and refining its therapeutic applications in the clinical management of chronic pain.