fMRI studies have linked placebo analgesia (PA) to alterations in neural activity in pain-related areas of the brain. Increases in PA over time are common, described as a self-reinforcing feedback mechanism. The present study tested the hypotheses that PA-related brain activity can be distinguished from nociceptive activation and that PA is a temporal derivative of the psychological processes occurring in the early stages of pain perception. GLM contrasts between placebo and natural history conditions revealed significantly greater PA-related activity in multiple regions (e.g., PAG, amygdala and ACC) (FDR= 0.05, p < 0.005). To examine the temporal development of PA, the time course (over 7 stimulus presentations) for each voxel was halved, leaving the fourth stimulus as a predictor of no interest. Several brain regions were significantly more active in the PA condition during the early stages of pain perception (FDR = 0.05, p < 0.0035). This study revealed several important facets related to the reduction and moderation of pain perception. Among the more important findings are: 1) placebo analgesia is associated with increased activity in emotion-related brain areas (e.g., amygdala), 2) changes to the psychological-set (e.g., anticipation) associated with a painful stimulus can alter pain perception, and 3) pain perception is temporally organized. The contextualization of a stimulus as (non)painful occurs early in the time course and is likely maintained via a self-reinforcing feedback mechanism.