Nocebo hyperalgesia induced by implicit conditioning

Background and objectives: Nocebo hyperalgesia (i.e., increased pain sensitivity based on expectations) can be induced by conditioning, but is supposed to be mediated by conscious expectation. Although recent evidence points to the feasibility of subliminal conditioning of nocebo hyperalgesia with masked faces, face processing might be a special case and the practical implications of subliminal conditioning remain questionable. This study aimed to implicitly condition nocebo hyperalgesia using supraliminal cues. Methods: Implicit differential nocebo conditioning (N = 48 healthy participants) was implemented by coupling high and low painful electric stimuli to varying visual stimuli that only differed in the symmetry/asymmetry of one component (CS + /CS-) and contained further distracting components. In the test phase, only the low painful stimulus followed both CS to test for conditioned nocebo effects in intensity and aversiveness ratings and electrodermal activity. A behavioral contingency test and a post-experimental questionnaire assessed contingency awareness. Results: A conditioned effect emerged in the aversiveness (p = .036; eta(2) = 0.09), but not in the intensity rating (p = .195) while controlling for contingency awareness. Further, increased skin conductance levels in response to CS + emerged, irrespective of contingency awareness (p = .014, eta(2) = 0.13). No conditioned responses in skin conductance responses emerged (p = .872). Limitations: Expected effects only emerged in part of the outcome variables. Conclusions: The results support the notion that implicit conditioning of nocebo hypoalgesia is feasible using a novel experimental conditioning design with supraliminal stimulus presentation, although further research is needed. So far, implicitly conditioned nocebo effects might have been underestimated despite vast clinical implications.