260 Lessons from the literature: impact of methodological focus in understanding nocebo hyperalgesia On the consistent measurement of relevant covariates As chapter 2 concluded, learning by experience, for example via classical conditioning, influences how pain is ultimately perceived, but which biobehavioral processes underlie this indirect outcome remained an open question. Our primary findings indicated that classical conditioning was more powerful and reliable in inducing nocebo effects, as compared to mere verbal suggestion of a negative outcome. As corroborated by our study in chapter 5, this indicates that when a negative effect is practically experienced, nocebo effects are stronger than when a negative outcome is only verbally communicated. While this may seem intuitive, it is valuable to produce an evidence-based verification, from studies across the board, that associative learning (the cognitive mechanism underlying classical conditioning 2–4) is the most powerful means for inducing nocebo effects on pain. In chapter 2 we also highlighted how multiple types of pain are influenced by negative learned associations, indicating that under nocebo hyperalgesic conditions, pain processing can lead to amplified pain responses regardless of the nature of the noxious stimulus. The finding that across different experimental paradigms, contexts, and types of pain, nocebo effects are consistently induced, is in line with novel perspectives of pain as a subjective and ever-changing experience. Nevertheless, our metaanalysis was unable to fully rely on current published research to address some crucial questions of interest on nocebo hyperalgesia, mainly due to methodological and logistical limitations. For example, the nocebo literature may face research challenges such as publication bias for significant findings, or the content and ecological validity of experimental models built to induce nocebo effects. Further on, we discuss the limitations posed by unpublished null or underwhelming results that are inaccessible to our literature review efforts, and we
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