Associations between placebo-responses across models and time: Exploratory analysis of a sham randomized clinical trial in chronic-back-pain patients.

BACKGROUND

Placebo-induced analgesia is a robust yet incompletely understood phenomenon. Despite extensive research, it remains unclear whether, and under what circumstances, the responsiveness to placebo can be generalized. This secondary exploratory analysis examined the generalizability of placebo-responses across time, pain-models (clinical and experimental) and scale context in a cohort of chronic-back-pain patients.

METHODS

Changes in clinical and experimental-pain were assessed following a single placebo injection. Clinical placebo-responses were defined as changes in self-reported pain-intensity from baseline to 30 min (immediate) and 24 h (prolonged) post-injection. Experimental placebo-responses were defined as changes in pressure pain thresholds, tolerance, and intensity from baseline to 30 min post-injection. In total, three clinical and four experimental placebo measures were assessed.

RESULTS

The mean age of participants (n = 113, 58 females) was 56.8 years (SD = 15.3). Significant placebo-response (d = 1.01, 95% CI [0.78, 1.23]), was observed in clinical but not experimental models. Associations between placebo-responses were significant and strongest within all clinical measures (Spearman's Rho: 0.201, p < .05;0.384, p < .01;0.634, p < .01), followed by weaker associations across the experimental measures (Spearman's Rho ranged from -0.120 to.271, with two significant correlations, p < .05 and p < .01). The weakest associations were observed between the clinical and experimental placebo-models (Spearman's Rho ranged from -0.004 to.269, with only one significant correlation, p < .05).

CONCLUSION

Based on this exploratory analyses, clinical placebo measures show stronger associations than experimental ones, with the weakest overlap between settings. The current findings are in line with the general notion that the placebo-response is highly affected by the context. This study was registered on Clinicaltrial.gov (protocol number NCT05994118).