This study investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. 77 healthy participants received nasal sprays (capsaicin for side effects or saline) believing they contained fentanyl before thermal pain. Results showed that nasal sprays with side effects led to lower pain, dependent on beliefs about side effects' relation to treatment outcome and treatment expectations. fMRI data indicated involvement of the descending pain modulatory system (anterior cingulate cortex and periaqueductal gray). Mild side effects can signal effective treatment, influencing expectations and outcomes via the descending pain modulatory system. This has implications for clinical practice and clinical trial design.

Lieven A. Schenk, Tahmine Fadai, Christian Büchel