Analgesic aftereffects of alpha high-definition transcranial alternating current stimulation over the DLPFC during experimental pain

High-definition transcranial alternating current stimulation (HD-tACS) targeting the dorsolateral prefrontal cortex (DLPFC) holds promise for pain management, though its neurobiological mechanisms remain unclear. This study aimed to investigate whether alpha HD-tACS applied to the left DLPFC modulates gamma oscillations to sustain analgesia during capsaicin-induced experimental pain (0.1% Capsaicin cream). Forty-five healthy participants underwent a single-blind, within-subject, sham-controlled protocol. EEG recordings were taken at three key time points: baseline (resting state), 5 minutes post-HD-tACS, and 15 minutes post-HD-tACS. Numeric rating scale (NRS) and oscillatory power changes were analyzed before, during, and after both active and sham stimulation. Results showed that active alpha HD-tACS significantly reduced NRS and area under curve (AUC) scores during both the stimulation period (0-30 minutes) and the post-stimulation period (30-60 minutes) compared to sham. EEG analyses revealed increased theta (4-7 Hz), alpha (8-13 Hz), beta(14-29 Hz), and low gamma (30-55 Hz) oscillations in the left DLPFC post-stimulation, but only low gamma oscillations passed the false discovery rate (FDR) correction. These findings suggest that alpha HD-tACS induces delayed analgesia by modulating low gamma oscillations in the DLPFC, highlighting its potential as a tool for optimizing non-invasive neuromodulation in pain therapy. The study bridges mechanistic insights with clinical outcomes, emphasizing the role of DLPFC low gamma activity in maintaining endogenous pain control.