Effects of Personalized Transcranial Alternating Current Stimulation (tACS) on Pain Perception

Background & Aims Neuropathic pain has been associated to alterations in ongoing oscillatory activity, particularly in the alpha band. Transcranial alternating current stimulation (tACS) offers a promising tool for modulating these oscillations, yet the widespread reliance on protocols with fixed stimulation frequencies has yielded limited and often contradictory findings on its efficacy for pain modulation. By personalizing tACS stimulation frequency on individual peak alpha frequency (IAF), this study aims to investigate how personalized tACS can modulate pain perception and pain related neural oscillations. Methods We recruited 38 healthy participants in a within subject sham-controlled double-blind study. To induce pain, we used sustained periodic 0.2 Hz thermonociceptive stimuli delivered to forearm of the dominant arm. tACS targeted M1, contralateral to the side of the thermonociceptive stimulation. The frequency of stimulation was set to the IAF. We measured painfulness rate (for periodic thermonociceptive stimuli) and heat pain thresholds (HPT) before and after tACS. Statistical tests were performed using linear mixed models using “time” (pre vs post) and “condition” (active vs sham) as factors. Results The decreased HPT values in the post-tACS phase suggest mild sensitization of the forearm. While the average values showed that tACS resulted in a less pronounced decrease in HPT, as well as a smaller increase in painfulness ratings compared to sham, these differences were not statistically significant. Nevertheless, the consistency of these trends across the different behavioral measures suggests a potential modulatory effect of tACS on nociception processing and pain perception. We further conducted an exploratory analysis to examine the influence of sex on tACS, Overall, the comparison of post-phase to pre-phase revealed a more pronounced effect in women than in men, with HPT showing the most significant decrease over time in women and no significant change in men. Additionally, there was a trend for an interaction effect, indicating that women responded better to tACS at SM-IAF. Conclusions These findings provide a novel perspective on advancing individualized neuromodulation approaches for neuropathic pain and beyond.