Beware of what you expect: a partial replication study on the behavioral and psychophysiological effects of negative expectations on mechanical hypersensitivity

Background. Increased mechanical sensitivity of uninjured skin surrounding a cutaneous injury is a sign of central sensitisation and can be induced in healthy individuals using high-frequency electrical stimulation (HFS). However, the role of negative expectations in developing mechanical hypersensitivity remains unclear. One prior study suggested that informing participants via written instructions that HFS would increase sensitivity led to more hypersensitivity compared to a control group. This study aimed to replicate those findings and extend the investigation with physiological measures. Methods. In a double-blind design, 60 participants were randomised to a control or nocebo group and underwent HFS on one forearm. We measured pinprick sensitivity, its spread, and pupil dilation (both resting and evoked by pinprick) to assess tonic arousal and phasic locus coeruleus activity. Results. While more participants in the nocebo group expected increased sensitivity, there were no significant differences in sensitivity increase, spread, or pinprick-evoked pupil dilation between groups. However, pupil dilation was greater following HFS, consistent with prior research. Conclusion. These results do not replicate previous behavioral findings suggesting that negative expectations enhance mechanical hypersensitivity after HFS. However, they confirm increased phasic locus coeruleus activity after HFS. Given that participants in the control group also expected sensitivity changes, we discuss these findings within current theories of expectations and provide guidance for future research.