54 While the number of itch studies included in this meta-analysis was small (8) compared to pain (30), overall effects on pain appear to be larger than those on itch across both learning methods, based on the present findings. Itch has been shown to be prone to suggestions and can be influenced by expectations 4 with one study that compared placebo effects induced with verbal suggestions for either pain or itch indicating that itch might be more prone to suggestions 38. Our finding that pain resulted in larger nocebo magnitudes across the studies included here, could suggest that compared to itch, the learning of pain associations may be facilitated to a larger degree. In other words, we speculate that, as pain is perhaps more threatening and aversive than itch, it may signal a more vital threat to the person and thereby, from an evolutionary perspective 37, result in stronger learning. Further research into nocebo effects is needed, however, to reach a sufficient sample size for reliable comparison results between pain and itch. The variability found in nocebo response magnitudes was not explained by differences between the type or intensity of pain or itch stimulation, or the length of learning. A moderate dispersion of effect sizes across the studies analyzed is important to note, especially when the measures that are systematically reported in studies, such as the duration of learning or the intensity of pain, are unable to explain such variability in nocebo response magnitudes. The large differences in applied experimental models of nocebo effects (e.g., different types of verbal suggestions, whether the experiment was conducted in a hospital or university setting, or types of nocebo and conditioned stimuli presented) may explain some of this variability in results 39. Similarly to the efforts for aligning experimental paradigms in animal models of disease 40,41, it is essential for the field of nocebo to focus on replicating experimental paradigms and aligning paradigms according to ecologically valid models that yield comparable results across studies.
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