Suppression of visceral nociception by C-fiber transmission block using temporal interference sinusoidal stimulation.

Introduction: Managing chronic visceral pain is challenging due to the lack of selective targeting of C-fiber nociceptors. Prior work has shown that suprathreshold dorsal root ganglia (DRG) stimulation (10-100 Hz) suppresses hypersensitivity and blocks colorectal afferent transmission through activity-dependent conduction slowing. Objective: To investigate the feasibility of temporal interference stimulation (TIS) for visceral pain management in mice. Methods: Temporal interference stimulation was delivered using 2 kilohertz-range sinusoidal currents (2,000 and 2,020 Hz) to create a 20-Hz envelope stimulus at focal regions. We utilized: (1) GCaMP6s imaging to visualize neuronal activation in the L6 DRG; (2) Single-fiber recordings to assess axonal blockade; (3) Visceromotor response (VMR) measurements to evaluate pain suppression, and (4) Immune profiling to monitor post-stimulation responses. Results: Temporal interference stimulation provided spatially adjustable activation of DRG neurons by shifting the focal interference zone. Low-frequency sinusoidal stimulation selectively blocked conduction in C-fibers and Aδ-fibers while sparing fast-conducting A-fibers. Notably, TIS reversibly suppressed VMR in both healthy and visceral hypersensitive mice. Furthermore, no immediate immune responses were detected in the DRG after treatment. Conclusion: Temporal interference stimulation on lumbosacral DRG offers a selective, spatially tunable method to block nociceptive transmission. These findings establish a robust foundation for developing TIS-based neuromodulation paradigms as a translational approach for improved chronic visceral pain management.