Transcranial Alternating Current Stimulation for Pain: Mixed Evidence and the Path to Precision Neuromodulation.

Neural oscillations are fundamental to the integration of sensory, affective, and cognitive processes that contribute to pain perception. Transcranial alternating current stimulation (tACS) provides a valuable tool for investigating and modulating these oscillatory dynamics. In this review, we examine the effects of tACS on pain perception and pain-related oscillations in both healthy participants and individuals with chronic pain, highlighting methodological variability and mechanistic uncertainties that may contribute to mixed findings. We identified 14 studies, including 9 studies of experimental pain in healthy individuals and 5 of clinical pain disorders, comparing tACS to sham. Somatosensory alpha was the most frequently targeted oscillatory feature. Results varied considerably. Several studies reported reductions in pain, increases in alpha power, or changes in sensorimotor and prefrontal connectivity, but others showed no meaningful neural or behavioral effects. Out of the 14 studies, 6 demonstrated analgesic benefits and 2 showed improvements only under specific conditions or within subgroups, for a total of 8/14 studies with positive findings. Possible sources of heterogeneity include variation in stimulation duration, electrode montage, frequency alignment with individual rhythms, contextual state, and anatomical and neurophysiological differences across individuals. Pre-registered studies with sufficient power are needed to replicate effects within the most promising intervention protocols to establish a foundation in the field. We also recommend inclusion of brain imaging or electrophysiological recordings to verify whether stimulation effectively modulates the targeted neural oscillations. Finally, recent methodological advances, including phase-specific tACS, amplitude-modulated tACS, and individualized electric-field modeling, offer new opportunities to enhance mechanistic precision and clinical applicability. We argue that by integrating these approaches, future research can move beyond fixed, one-size-fits-all protocols toward personalized, state-dependent, closed-loop tACS approaches. Exploring these frontiers will transform tACS from an exploratory tool into a reliable intervention for pain.