Associations Between Interindividual Differences, Expectations and Placebo and Nocebo Effects in Itch

Abstract

Introduction: Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent.Methods: The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; n = 92) or negative VSs (Studies 2+3; n = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses.Results: The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower.Conclusion: Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.

Placebo–Placebo, Nocebo–Nocebo, Placebo–Nocebo, and Nocebo–Placebo Effects: A Review of Eastern and Western Perspectives

“…For instance, a patient with chronic back pain seeks treatment from an Ayurvedic practitioner who prescribes herbal remedies, dietary changes, mindfulness meditation, and positive affirmations (Torstensen, T. A. (1996); Ondrejkovicova, A., Petrovics, G., Svitkova, K., & Balogh, V. (2017); S, M., Wele, A., Patgiri, B. J., & Porszasz, PLACEBO/NOCEBO EFFECT CATEGORIES FROM EASTERN AND WESTERN PERSPECTIVES mechanisms, and past experiences (Bagarić et al, 2022;Meeuwis et al, 2021). These factors can influence an individual's susceptibility to negative expectations thereby associating themselves leading to classical conditioning leading to indirect-direct appearance of classical conditioning (refer 4).…”

A Narrative Review of Placebo and Nocebo Effects on Itch

“…12 An additional analysis of previous trials (Studies 8, 9 and 11; Table 2) was conducted by S. Meeuwis et al, and published in 2021. 13 Innovative statistical methods were applied to determine the interindividual differences on how placebo effects are formed. 13 The researchers reported that the effects of open-label positive and negative verbal suggestions on itch may be more dependent on its expectation, while the closed label approach would directly influence the itch.…”

“…13 Innovative statistical methods were applied to determine the interindividual differences on how placebo effects are formed. 13 The researchers reported that the effects of open-label positive and negative verbal suggestions on itch may be more dependent on its expectation, while the closed label approach would directly influence the itch. 13 Furthermore, the researchers determined that low sensitivity to rewards and high ignorance of bodily signals were associated with increased placebo response to verbal suggestion.…”

“…13 Furthermore, the researchers determined that low sensitivity to rewards and high ignorance of bodily signals were associated with increased placebo response to verbal suggestion. 13…”

Risk factors associated with nocebo effects: A review of reviews

“…Such outcomes were described by Hahn as nocebo effects ( Hahn, 1997 ), which were distinguished from ‘placebo side effects’, whereby a treatment primarily intended as beneficial can cause harmful outcomes. This is the case of nocebo side effects, namely, unpleasant symptoms that arise following a treatment that is primarily intended as beneficial, but of which specific side effects are anticipated ( Meeuwis et al, 2021 ). Notably, recent evidence suggests that primary manipulations of nocebo and nocebo side effects do not produce equivalent results.…”