Placebo Hypoalgesia and Nocebo Hyperalgesia Induced by Observational Learning May Be Difficult to Disentangle in a Laboratory Setting.

Observational learning (OBL) (seeing pain/pain treatment in others) can evoke placebo hypoalgesia and nocebo hyperalgesia. Data that compare these effects and illuminates the role of expectations and empathy are scarce. Healthy participants (n = 105) were randomized to: 1) placebo OBL, 2) nocebo OBL, or 3) no-observation control group. OBL consisted of a model simulating pain relief or increase after a sham ointment was applied to one arm. Pain was evoked with thermal stimuli on both arms (ointment, contralateral) at baseline and postobservation. Expectations, pain ratings, and physiological data (eg, skin conductance level) were collected. A 3 × 2 × 2 (Group × Arm × Phase) mixed analyses of variance revealed a 3-way interaction that confirmed that OBL modulates pain: F(2, 93) = 6.08, P = .003, ηp2 = .12. Significant baseline-to-post-observation pain increases were shown in the nocebo OBL group, with a bigger increase for the arm with ointment (both P ≤ .007). In the placebo OBL group, pain was higher for the contralateral relative to the ointment arm (P < .001). Baseline-to-post-observation pain increase was significant for the contralateral arm (P < .001). Expectation mediated these effects. Skin conductance level decreased over time during ointment trials in the nocebo OBL group, suggesting reduced physiological arousal. The findings illustrate that OBL modulates pain through expectations. In the placebo OBL group, the pain did not decrease for the ointment but increased for the contralateral stimuli, which may reflect nocebo learning. Experimental OBL paradigms typically examine relative differences between ointment and contralateral cues. This can complicate disentangling placebo hypoalgesia and nocebo hyperalgesia in laboratory settings. Implications for existing theories are discussed. PERSPECTIVE: Data that systematically compare placebo hypoalgesia and nocebo hyperalgesia induced by OBL are scarce. The current work illustrates that these effects may be more difficult to disentangle than previously assumed, which could have implications for existing theories on OBL and placebo effects and their translation to clinical practice.

Pain Rating is Worth a Thousand Words: Nocebo Hyperalgesia Induced by Verbal Modeling Prevails Over the Effects of Symbolic Modeling and Verbal Suggestion.

This study compares the effectiveness of verbal modeling, symbolic modeling, and verbal suggestion in inducing nocebo hyperalgesia. It is the first study to examine the contribution of stress to observationally induced nocebo hyperalgesia. This study's experimental groups represented various sources of social information: a group of people participating in the study (verbal modeling), a single participant (symbolic modeling), and an experimenter (verbal suggestion). During the experiment, participants received electrocutaneous stimuli at the same intensity, some of which were applied with a nocebo (sham device). Participants in the verbal modeling group were acquainted with pain ratings that had allegedly been provided by other participants. The ratings suggested that other participants experienced more pain in the nocebo trials than in the control trials. In the symbolic modeling group, participants observed a videotaped model experiencing more pain in the nocebo than in the control trials. In the verbal suggestion group, participants received a verbal suggestion of hyperalgesia in the nocebo trials and no suggestion in the control trials. No manipulations were used in the control group. To investigate whether nocebo hyperalgesia is stable over time, an additional extinction phase was conducted. Nocebo hyperalgesia was induced by verbal modeling only and was partially mediated by expectancy. Stress was a significant moderator of the induced effect. Nocebo hyperalgesia was extinguished during the extinction phase. The obtained results provide potential implications for minimizing nocebo hyperalgesia in clinical practice by, for instance, controlling patients' expectancies and stress levels. PERSPECTIVE: The study shows the role of pain-related information derived from other people in shaping negative treatment experiences in the individual. Because information from others has a particular impact on individuals experiencing stress, both this information and the stress level of patients should be monitored in the treatment process.