Differential Classical Conditioning of the Nocebo Effect: Increasing Heat-Pain Perception without Verbal Suggestions
Bibliographic record
Abstract
Background: Nocebo effects, including nocebo hyperalgesia, are a common phenomenon in clinical routine with manifold negative consequences. Both explicit expectations and learning by conditioning are known to induce nocebo effects, but the specific role of conditioning re-mains unclear, because conditioning is rarely implemented independent of verbal suggestions. Further, although pain is a multidimensional phenomenon, nocebo effects are usually assessed in subjective ratings only, neglecting, e.g., behavioral aspects. The aim of this study was to test whether nocebo hyperalgesia can be learned by conditioning without explicit expectations, to assess nocebo effects in different response channels, and to exploratively assess, whether contingency awareness is a necessary condition for conditioned nocebo hyperalgesia. Methods: Twenty-one healthy volunteers were classically conditioned using painful and non-painful heat stimuli that followed two different cues. The conditioned nocebo effect was as-sessed by subjective ratings of perceived stimulation intensity on a visual analogue scale and a behavioral discrimination task, assessing sensitization and habituation in response to the same stimulation following the two cues. Results: Results show a conditioned nocebo effect indicated by the subjective intensity ratings. Conditioned effects were also seen in the behavioral responses, but paradoxically, be-havioral responses indicated decreased perception after conditioning, but only for subjects successfully conditioned as indicated by the subjective ratings. Explorative analyses suggested that awareness of the contingencies and the different cues was not necessary for successful conditioning. Conclusions: Nocebo effects can be learned without inducing additional explicit expectations. The dissociation between the two response channels, possibly representing the condi-tioned and a compensatory response, highlights the importance of considering different out-comes in nocebo responses to fully understand underlying mechanisms. The present results challenge the role of explicit expectations in conditioned nocebo effects and are relevant with implications in clinical contexts, e.g., when transient adverse effects become conditioned.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".