The magnitude of placebo analgesia effects depends on how they are conceptualized

Objective: Placebo effects are usually calculated as the difference between placebo treatments and no treatments. Recently, placebo-like effects have been investigated using open and hidden administrations of active treatments. The aim of the study was to directly compare the two types of placebo effects and examine how they are influenced by personality traits. Methods: In a within-subject, randomized, blinded, balanced placebo trial design study with 48 healthy volunteers, we compared placebo and placebo-like effects and tested if expectancy, absorption and suggestibility correlated with these effects. Subjects completed the Tellegen Absorption Scale and the Sensory Suggestibility Scale, and pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections of hypertonic saline with lidocaine or matching placebo in randomized order: open treatment, hidden treatment, placebo and control. The placebo effect was defined as the difference in pain between the placebo and the control condition and the placebo-like effect as the difference in pain between the open and hidden condition. Results: Placebo effects were significant both in the traditional paradigm: mean placebo effect AUC 1626 mm2 (95% CI 958-2293) and the open-hidden paradigm: mean placebo-like effect AUC 801 mm2 (95% CI 134-1469), but there was a significant difference between the magnitude of the two effects (p = 0.049). Absorption and suggestibility did not predict the placebo or the placebo-like effect. Estimated expected pain relief correlated with placebo effects but not placebo-like effects. Conclusion: The magnitude of placebo effects differs depending on how they are conceptualized and calculate