Objective: Expectancies are known to shape pain experiences, but it remains unclear how different types of expectancies contribute to daily pain fluctuations in fibromyalgia. This combined experimental and diary study aims to provide insights into how experimentally-derived nocebo hyperalgesia and other, diary-derived, expectancy-related factors are associated with each other and with daily pain in fibromyalgia. Methods: Forty-one female patients with fibromyalgia first participated in a lab procedure measuring nocebo hyperalgesia magnitude, then filled out an electronic diary 3 times a day over 3 weeks regarding the expectancy-related factors of pain expectancy, anxiety, optimism, and pain-catastrophizing thoughts, and current pain intensity. Results: Our results indicate that experimentally-induced nocebo hyperalgesia was not significantly related to diary-assessed expectancy-related factors and did not predict daily fibromyalgia pain. Higher levels of the self-reported expectancy-related factors pain expectancy and pain catastrophizing, but not anxiety and optimism, predicted moment-to-moment pain increases in fibromyalgia, after controlling for current pain, moment-of-day and all other expectancy-related factors. Conclusion: Our exploratory research findings indicate that self-reported expectancy-related factors, particularly pain expectancy and pain catastrophizing, are potentially more relevant for predicting daily pain experience than experimentally-induced nocebo hyperalgesia. Further translation of nocebo hyperalgesia is needed from experimental to Ecological Momentary Assessment research. Our findings imply that targeting the decrease in pain expectancy and catastrophizing thoughts e.g., via Cognitive Behavioral Therapy, have potential for improving daily pain levels in fibromyalgia.

Nocebo effects on pain are widely thought to be driven by negative expectations. This suggests that anticipatory processing, or some other form of top-down cognitive activity prior to the experience of pain, takes place to form sensory-augmenting expectations. However, little is known about the neural markers of anticipatory processing for nocebo effects. In this event-related potential study on healthy participants (n = 42), we tested whether anticipatory processing for classically conditioned nocebo-augmented pain differed from pain without nocebo augmentation using stimulus preceding negativity (SPN), and Granger Causality (GC). SPN is a slow-wave ERP component thought to measure top-down processing, and GC is a multivariate time series analysis used to measure functional connectivity between brain regions. Fear of pain was assessed with the Fear of Pain Questionnaire-III and tested for correlation with SPN and GC metrics. We found evidence that both anticipatory processing measured with SPN and functional connectivity from frontal to temporoparietal brain regions measured with GC were increased for nocebo pain stimuli relative to control pain stimuli. Other GC node pairs did not yield significant effects, and a lag in the timing of nocebo pain stimuli limited interpretation of the results. No correlations with trait fear of pain measured after the conditioning procedure were detected, indicating that while differences in neural activity could be detected between the anticipation of nocebo and control pain trials, they likely were not related to fear. These results highlight the role that top-down processes play in augmenting sensory perception based on negative expectations before sensation occurs.