Experience with opioids does not modify the brain network involved in expectations of placebo analgesia

Placebo analgesia (PA) is defined as a psychobiological phenomenon triggered by the information surrounding an analgesic drug instead of its inherent pharmacological properties. PA is hypothesized to be formed through either verbal suggestions or conditioning. The present study aims at disentangling the neural correlates of expectations effects with or without conditioning through prior experience using the model of PA. We addressed this question by recruiting two groups of individuals holding comparable verbally‐induced expectations regarding morphine analgesia but either (i) with or (ii) without prior experience with opioids. We then contrasted the two groups' neurocognitive response to acute heat‐pain induction following the injection of sham morphine using electroencephalography (EEG). Topographic ERP analyses of the N2 and P2 pain evoked potential components allowed to test the hypothesis that PA involves distinct neural networks when induced by expectations with or without prior experience. First, we confirmed that the two groups showed corresponding expectations of morphine analgesia (Hedges' g ( s ) < .4 positive control criteria, g ( s ) = .37 observed difference), and that our intervention induced a medium‐sized PA (Hedges' g ( av ) ≥ .5 positive control, g ( av ) = .6 observed PA). We then tested our hypothesis on the recruitment of different PA‐associated brain networks in individuals with versus without prior experience with opioids and found no evidence for a topographic N2 and P2 ERP components difference between the two groups. Our results thus suggest that in the presence of verbally‐induced expectations, modifications in the PA‐associated brain activity by conditioning are either absent or very small.