Analgesic effects of high-frequency rTMS on pain anticipation and perception

Previous studies suggest that pain perception is greatly shaped by anticipation, with M1 and DLPFC involved in this process. We hypothesized that high-frequency rTMS targeting these regions could alter pain anticipation and thereby reduce pain perception. In a double-blind, sham-controlled study, healthy participants received 10 Hz rTMS to M1, DLPFC, or a sham treatment. Assessments were conducted before, immediately after, and 60 min after stimulation, including laser-evoked potentials, pain ratings, and anticipatory EEG. M1-rTMS immediately reduced laser-evoked P2 amplitude, increased sensorimotor high-frequency α-oscillation power, and accelerated peak alpha frequency in the midfrontal region during pain anticipation. In contrast, DLPFC-rTMS reduced the N2-P2 complex and pain ratings 60 min post-stimulation, an effect associated with prolonged microstate C duration during pain anticipation-a microstate linked to default mode network activity. Thus, M1-rTMS immediately modulates anticipatory α-oscillations and laser-evoked potentials, while DLPFC-rTMS induces delayed analgesic effects partially by modulating default mode network activity.