Papers of the Week

Clinical evidence indicates dorsal root ganglion (DRG) stimulation effectively reduces pain without the need to evoke paresthesia. This paresthesia-free anesthesia by DRG stimulation can be promising to treat pain from the viscera, where paresthesia usually cannot be produced. Here, we explored the mechanisms and parameters for DRG stimulation using an ex vivo preparation with mouse distal colon and rectum (colorectum), pelvic nerve, L6 DRG, and dorsal root in continuity. We conducted single-fiber recordings from split dorsal root and assessed the effect of DRG stimulation on afferent neural transmission. We determined the optimal stimulus pulse width by measuring the chronaxies of DRG stimulation to be below 216 µsec, indicating spike initiation likely at attached axons rather than somata. Sub-kilohertz DRG stimulation significantly attenuates colorectal afferent transmission (10, 50, 100, 500 and 1000 Hz), of which 50 and 100 Hz show superior blocking effects. Synchronized spinal nerve and DRG stimulation reveals a progressive increase in conduction delay by DRG stimulation, suggesting activity-dependent slowing in blocked fibers. Afferents blocked by DRG stimulation show a greater increase in conduction delay than unblocked counterparts. Mid-range frequencies (50-500 Hz) are more efficient at blocking transmission than lower or higher frequencies. In addition, DRG stimulation at 50 and 100 Hz significantly attenuates in vivo visceromotor responses to noxious colorectal balloon distension. This reversible conduction block in C- and Aδ-type afferents by sub-kilohertz DRG stimulation likely underlies the paresthesia-free anesthesia by DRG stimulation, thereby offering a promising new approach for managing chronic visceral pain.