Transcranial Alternating Current Stimulation at Alpha Frequency Reduces Pain When the Intensity of Pain is Uncertain

•Transcranial alternating current stimulation (tACS) at alpha frequency affects pain.•Alpha tACS over somatosensory regions compared with sham lowered perceived pain.•However, uncertainty about pain intensity moderated this effect.•Perceived pain was lower during alpha tACS, only when pain intensity was uncertain.•Alpha tACS has the potential to alleviate pain, particularly when pain is uncertain. Alpha activity directly before pain onset has been implicated in pain experience with higher prestimulus alpha associated with lower reported pain. However, expectations about pain intensity also seem to affect prestimulus alpha activity. To date, evidence for a relationship between alpha activity and pain experience has been largely correlational. Transcranial alternating current stimulation at alpha frequency (alpha tACS) permits direct manipulation of alpha activity and therefore an examination of the potential causal relationship between alpha activity and pain. We investigated whether somatosensory alpha tACS could reduce pain experience and whether this was influenced by uncertainty about pain intensity. In a within-subjects design, perceived pain intensity and unpleasantness were assessed in 23 participants during alpha tACS and sham stimulation. Visual cues preceding the pain stimulus were used to manipulate uncertainty. A significant tACS × Uncertainty × Stimulus intensity interaction was found for reported pain intensity (F2,44 = 4.50, P = .017, partial η2 = .17) and unpleasantness (F1,22 = 4.78, P = .040, partial η2 = .18). Pain experience during the application of somatosensory alpha tACS was significantly lowered compared with sham stimulation, but only when the intensity of an upcoming stimulus was uncertain. To our knowledge, this is the first study to suggest that somatosensory alpha tACS might lead to a reduction in pain. Interventions targeting alpha activity may have the potential to alleviate chronic pain. However, a patient's expectation about the intensity of upcoming pain must also be taken into account.