The onset and offset of noxious stimuli robustly modulate perceived pain intensity

Abstract Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. This is typically evoked using a three-step noxious heat stimulus. In other clinical and laboratory settings, prior pain experience may increase pain intensity as well. Therefore, we hypothesized that even small increases in stimulus intensity within the noxious range would be accompanied by enhanced reported pain intensity. To test this possibility, we inverted the intensity order of the three-step stimulus, so that the same hot temperature is immediately preceded by an increase from a transiently lowered temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity during the novel, inverted, three-step stimulus. This disproportionate increase is similar in magnitude to that of offset analgesia. Control stimuli demonstrate that these changes in pain intensity are distinct from habituation. The magnitudes of offset analgesia and the disproportionate increase in pain intensity correlate with each other but not with the absolute noxious stimulus temperature. These observations suggest that the disproportionate increase in pain intensity represents an “onset hyperalgesia.” Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study finds that perceptual enhancement of noxious stimulus change occurs bidirectionally and that this depends on the intensity and direction of change of the immediately preceding stimulus.