Placebo hypoalgesia and nocebo hyperalgesia induced by observational learning may be difficult to disentangle in a laboratory setting

Observational learning (OBL) can evoke placebo hypoalgesia and nocebo hyperalgesia, however, these effects have rarely been systematically compared. Healthy participants (n=105) were randomised to: 1) placebo OBL, 2) nocebo OBL, or 3) a no-observation control group. During OBL, a videotaped model simulated pain relief or increase after a sham ointment was applied. Thermal pain was evoked on two arms (ointment, control) at baseline and post-OBL. A three-way interaction confirmed that OBL modulates pain: F(2,93)=6.08, p=.003, ηp2=.12. Pain increased after nocebo OBL, with a bigger increase for the ointment arm (both p≤.007). After placebo OBL, pain increased for the control arm only (p<.001). Expectations mediated these effects. That pain for the control stimuli increased after placebo OBL could reflect nocebo learning. Experimental paradigms typically examine relative differences between ointment and control stimuli. Our results show that this can complicate disentangling placebo hypoalgesia and nocebo hyperalgesia in laboratory settings.