Preemptive transcranial direct current stimulation mitigates susceptibility to persistent pain.

Transcranial direct current stimulation (tDCS) exhibits potential for pain management, yet its protective efficacy against persistent pain remains underexplored. This study investigates the protective effects of preemptive tDCS over the primary motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) on mitigating capsaicin-induced persistent pain. Eighty participants underwent M1- or dlPFC-targeted tDCS before capsaicin application, with electroencephalography recorded for 60 min. Both protocols comparably reduced pain intensity, anxiety, and sensorimotor β/γ-oscillation activity. Microstate analysis identified five canonical microstates (A - E) that have been linked to auditory, visual, default-mode, dorsal attention, and salience networks. M1-tDCS decreased microstate C (self-referential processing) while enhancing microstate D (cognitive control), whereas dlPFC-tDCS suppressed microstate D activity. Mechanistically, M1-tDCS alleviated anxiety via increased D ↔ E transitions (cognitive-emotional integration), while dlPFC-tDCS attenuated pain through reduced D ↔ C shifts (cognitive-self-referential integration). These findings highlight both shared and distinct neuromodulatory effects of M1/dlPFC-tDCS, supporting their potential as preemptive strategies for persistent pain management.