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

Abstract

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. High-frequency rTMS to M1 and DLPFC modulates pain anticipation and perception. M1-rTMS immediately reduced pain via α-oscillation modulation, while DLPFC-rTMS produced delayed analgesia through default mode network modulation.