Supplementary Material for: Positive Treatment Expectancies Reduce Clinical Pain and Perceived Limitations in Movement Ability Despite Increased Experimental Pain: A Randomized Controlled Trial on Sham Opioid Infusion in Patients with Chronic Back Pain

Background: Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects. Objectives: We investigated to what extent a sham opioid infusion (saline solution) produces sustained clinically relevant placebo and nocebo effects in chronic back pain patients. Methods: Fifty-nine patients received the sham opioid infusion applied via a large drain dressing and were compared to 14 control patients without intervention (natural history, NH) while experimental pain stimuli were applied. All subjects were told that the infusion would decrease pain although in rare cases pain increase would be possible (induction of expectancy). In addition, conditioning was introduced where the participants either experienced a decrease in experimental pain (n = 17; placebo conditioning), an increase (n = 21; nocebo conditioning), or no change (n = 21, no conditioning). Results: Compared to the NH group, all infusion groups showed positive treatment expectancies and significantly (p < 0.001) reduced clinical back pain (primary outcome) and pain-related disability (secondary outcome, assessed by self-reported functional capacity and perceived impairment of mobility). Even the nocebo conditioned group experiencing increased experimental pain developed positive treatment expectancies followed by reduced pain experience. Positive treatment expectancies and relief in clinical back pain were significantly positively correlated (r = 0.72, p < 0.01). Conclusions: These findings suggest that it may be beneficial to explicitly shape and integrate treatment expectancies into clinical pain management.