Alpha transcranial alternating current stimulation modulates pain anticipation and perception in a context-dependent manner.

Abstract: Pain perception is closely tied to the brain's anticipatory processes, particularly involving the suppression of sensorimotor α-oscillations, which reflect the system's readiness for incoming pain. Higher sensorimotor α-oscillation levels are correlated with lower pain sensitivity. Alpha transcranial alternating current stimulation (α-tACS) can enhance these oscillations, potentially reducing pain perception, with effects that may be sustained and influenced by the certainty of pain expectations. Hence, this study investigated the immediate and sustained effects of α-tACS on pain anticipation and perception, focusing on how these effects are shaped by the certainty of expectations. In a double-blind, sham-controlled design, 80 healthy participants underwent a 20-minute session of real or sham α-tACS over the right sensorimotor region. Behavioral and neural responses related to pain anticipation and perception were recorded before, immediately after, and 30 minutes poststimulation under both certain and uncertain conditions. Compared with sham stimulation, real α-tACS disrupted the habituation of laser-evoked potentials (N2-P2 complex), particularly under certain expectations, with effects persisting 30 minutes poststimulation. In anticipatory brain oscillations, real α-tACS enhanced somatosensory α1-oscillations and increased midfrontal θ-oscillations in conditions of certainty, with θ-oscillation modulation showing sustained effects. Mediation analysis revealed that α-tACS reduced pain reactivity by enhancing somatosensory α1-oscillations but increased pain reactivity through the enhancement of midfrontal θ-oscillations, with the latter effect being more pronounced. These findings suggest that while α-tACS may provide pain relief through somatosensory α-oscillation augmentation, its stronger and longer-lasting impact on midfrontal θ-oscillations could lead to hyperalgesia, particularly in the context of certain pain expectations.