Response of dorsal horn neurons in mice to high‐frequency (kHz) biphasic stimulation is not sensitive to local temperature rise

Clinically accepted for treatment of chronic pain 10 kHz-frequency electric spinal cord stimulation (10 kHz-SCS) releases more power in tissue compared to conventional low-frequency (<100 Hz) stimulation due to increased duty cycle. This is equivalent to the release of more heat in a surrounding tissue, which may change the functional state of affected neural elements. In the case of SCS, plausible candidates to be affected by thermal a component of kHz-frequency electric field stimulation (kHz-FS) are dorsal column axons and neurons of the superficial layers of the dorsal horn. In this study, we tested the hypothesis that joule heat produced by kHz-FS modulates neuronal excitability. In slices of the mouse spinal cord, we monitored membrane potential and membrane input resistance in neurons of lamina II during exposure to kHz-FS. Surprisingly, we found no correlation between temperature rise and changes of membrane parameters. Furthermore, the depolarizing effect of kHz-FS was always immediate and remained persistent throughout stimulation, whereas rise of temperature was delayed for 1-2 s and reached its saturation level within the following few seconds. Thus, we concluded that the thermal component has an insignificant role in the mechanism of kHz-FS action.