Chapter 2 – Meta-analysis 55 One of the most consistent differences between experimental nocebo studies seems to be the type of verbal suggestion delivered to participants. No two studies administered the same verbal suggestion. Different verbal suggestions could contain distinct emotional loads and be perceived as more or less threatening, which may in turn influence nocebo responses 13,17. While beyond the scope and reach of the current meta-analysis, a future systematic review of distinct verbal suggestions, for example using content analysis approaches borrowed from linguistics 42,43, could shed a light on how different verbal suggestions could impact nocebo responses. There are other variables that could explain variability of induced nocebo responses, such as sampling, demographics, and the inclusion criteria for participation, but a limitation is that these factors are not consistently reported in papers and could not be investigated in the current meta-analysis. Additionally, studies do not systematically measure fear, which is shown repeatedly to be involved in nocebo responses 13,17,44–46. Other variables relevant to the emotional context of studies, such as the demeanor of the experimenter 47 or whether the experiment is set in an academic building or hospital, are also often not clearly documented, and could not be analyzed here. Finally, risk of bias was low across all studies and showed no relationship to nocebo magnitudes. However, the assessment tool used for this meta-analysis is designed for quantitative sensory testing studies 23 but could have missed bias aspects, such as potential publication bias for significant results, which meta-analyses studies should consider addressing. This systematic review and meta-analysis quantified magnitudes of nocebo responses on cutaneous sensations (pain and itch) for distinct learning paradigms in experimental studies (classical conditioning with verbal suggestion, or verbal suggestion alone). We replicated previous findings that classical conditioning combined with negative verbal suggestions was strongest for inducing nocebo responses on pain.
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