AbstractPredicting that a stimulus is painful facilitates action to avoid harm. But does the prediction of upcoming painful events engage the same or different processes than acting to avoid or reduce current pain? In this fMRI experiment, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, and the ability of voluntary action to affect the duration of the upcoming stimulation. Participants (n = 30) performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Participants’ task was to press a response button within a short time window upon the presentation of a response cue during S1. On action-effective trials, pressing the button within the specified time window reduced the duration of the upcoming stimulation. On action-ineffective trials, pressing the button had no effect on upcoming stimulation. Predicted pain increased activation in regions including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Region-of-interest analyses revealed that insula’s responses for predicted pain were also modulated by potential action consequences, especially in the left hemisphere, albeit without a direct relationship with motor output. Taken together, these findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead depends on the consequences of that stimulus for sensorimotor control of behavior.Significance statementDuring acute pain, the processing of an acute sensory event likely occurs in parallel with predictive processing about its relevance for current and upcoming voluntary behavior. Here, we temporally separated the functional processes underlying current and predicted pain and found that activation in regions typically implicated in acute pain is modulated both by the noxious nature of upcoming events, as well as by the possibility to affect those events via voluntary action. Specifically, activation in anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula during the delivery of a painful or nonpainful stimulus was modulated by whether an upcoming stimulus would be painful. Furthermore, ACC/MCC involvement in pain prediction depended on whether a meaningful action was performed, i.e., whether a button-press action would reduce the duration of the upcoming stimulus. Although insula activation was also affected by the possibility of the button-press action to reduce the duration of the upcoming stimulation, only MCC had a direct relationship with motor output.