Chapter 8 – General discussion 261 expand on concerns emerging from chapter 2 regarding experimental modeling approaches. Other wider methodological considerations arising from this project concern the choice of measures and paradigms in pain research. In our meta-analysis, overall magnitudes of nocebo responding could not be explained based on any of the measures that we collected from the experimental studies included. It appears that, no matter the number of learning trials, the type of sensation, or any other obtainable factor, nocebo effects up to 2.5 points magnitude (out of 10) can be obtained, with no one factor moderating this variability. This finding opened questions for future research relating to the variables that we were not able to obtain from previous studies. For example, while some important factors that influence nocebo have only incidentally been studied (see for example a study by Tinnerman and colleagues 5), using more consistent methods in experimental models, as well as consistent in- and exclusion criteria, may provide a more stable platform on which nocebo magnitudes can be assessed and compared between studies. Additionally, measuring fear levels and reporting in detail the intensities of administered pain may point us towards potentially stronger moderators of nocebo magnitudes. Implications for biobehavioral nocebo research Methodological challenges may be of particular importance in biobehavioral and neuroimaging research into nocebo hyperalgesia. The neurobiological foundations of nocebo hyperalgesia are characterized by an apparent intricacy and consistency as well as replicability are central in understanding and tackling negative learned effects. Chapter 3 presents a comprehensive review of the neurobiological underpinnings of nocebo hyperalgesia, with a focus on neuroimaging. Much of what we know about pain perception is based on self-reported pain levels.
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