We performed five BOLD-fMRI measurements in healthy volunteers during prolonged heat pain stimulation to investigate the consistency of brain region specific activation and temporal alterations of brain activation. Left and right insula showed pain related activation in all volunteers and the highest activation values in the left insula at the beginning of the experiment. Compared to the insular regions, ACC and precuneus revealed higher BOLD signal variations during 11 min of noxious stimulation. The findings can be interpreted as region specific habituation effects on pain processing in the human brain.