Individual differences in response to repeated painful stimulation: Habituation, sensitization, and nocebo effects

Abstract

The present study analyzes habituation, sensitization, and nocebo effects based on individual differences in response to painful stimulation. Habituation and sensitization to pain show two opposite patterns that may occur during repeated painful stimulation. Negative expectations such as a nocebo manipulation have been shown to increase pain ratings, but it is unclear to what extent they can influence habituation and sensitization to pain. In this preregistered study, we investigate the effects of repeated painful stimulation across time with pain intensity and unpleasantness ratings, individual differences in the response trajectories, and the impact of a nocebo manipulation in the context of habituation and sensitization response subgroups. We included 60 participants (26 male, 34 female, age 18–60) who received repeated painful electrical stimulation across four runs. Half of the participants received a negative verbal expectation (i.e., nocebo manipulation) after the third run. Participants provided both intensity and unpleasantness ratings after each stimulus. The results demonstrated large individual variability in responses. On the group level, participants showed sensitization to pain which decreased across runs. Individual slopes across and within-runs varied greatly, starting with mostly sensitization and ending with habituation profiles. Habituation of pain intensity and unpleasantness was highly correlated. The nocebo manipulation resulted in a significant nocebo effect, demonstrating a large increase in pain and unpleasantness ratings. In summary, this study showed large individual differences and the impact of a nocebo manipulation on the background of different response profiles.

Perspective

Repeated painful stimulation resulted in patterns of habituation and sensitization, with large individual variability that differed for across and within-run analyses. Pain intensity and unpleasantness ratings were highly correlated. A nocebo manipulation demonstrated increased intensity and unpleasantness reports, even after habituation and sensitization patterns were established.