Peripheral neuromodulation can relieve pain through sensory activation or conduction block. However, electrical stimulation of mixed nerves couples these intended effects to unwanted neural activity. Here we demonstrate local cooling can separate targeted from off-target neural activity. In the rat sciatic nerve, precooling reduced the onset response to kilohertz-frequency stimulation by about 90% and maintained block in the target pathway during rewarming. During low-frequency stimulation, spatially graded cooling suppressed A{delta} enriched activity and blocked nontarget propagation. This produced a directional, A{beta} biased afferent output. A cooling-electrical neural digital twin predicted both responses and linked them to field-edge transition dynamics and spatially separated control of recruitment and conduction. These findings provide a mechanistically grounded route beyond the targeting limits of electrical stimulation alone.
Yang, S., Yu, X., Yang, S., Wang, Q., Bi, G.-Q., Liu, Y., Du, Z.
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