Expectations, conditioning, and the placebo effect do not differ between fibromyalgia patients and healthy controls but might be differently associated

Introduction: Individuals with chronic pain such as fibromyalgia (FM) are often experiencing disappointing outcomes from clinical therapies, which theoretically should condition them to experience low placebo analgesia. However, no consistent differences in the placebo effect were found between healthy controls (HC) and chronic pain patients. This study examined the expectations, conditioning, and placebo effect in HC and FM, and the relationships between these factors in both groups. Methods: Female HC and FM patients were recruited, provided demographic and clinical information and underwent the experimental placebo paradigm. This paradigm has the advantage of measuring expectations (baseline, reinforced, and after placebo), conditioning, and placebo effect. Mixed factorial ANCOVAs, correlational analysis, stepwise and moderation regression analysis were employed. Results: Thirty-seven HC and 32 FM patients participated. Three Mixed factorial ANCOVAs showed no main effects of group or interactions for expectations (p = .692), conditioning (p = .357), or placebo effect (p = .819). Reinforced expectations predicted the conditioning strength (r = .48, p = .008) and placebo effect (r = .44, p = .014) in HC but not in FM participants. In FM, duration of pain predicted the reinforced expectations (r = −.38, p = .035) and moderated the prediction of the placebo effect by the conditioning strength (b = .04, p = .011). Conclusion: While the classical placebo theorem is supported in healthy controls, with conditioning influencing expectations, which in turn predict the placebo effect, these associations are not observed in fibromyalgia, where prior clinical experience plays a more significant role. These findings underscore the impact of previous negative clinical experiences on the placebo effect and, possibly, on responses to effective treatments.