Mia Thomaidou

48 Classical conditioning and verbal suggestions in pain and itch A range of different verbal suggestions were used to induce nocebo responses on pain and itch. Most studies used either an inert cream or inactive electrodes as the nocebo stimulus that would supposedly increase pain/itch sensitivity. For example, studies suggested to participants that their pain will be increased upon the activation of electrodes on their skin because these electrodes “enhance the conductivity of the pain signal being sent to the brain” 29 or “the cream that will be applied to your arm increases the effect of the heat pain and you will feel more pain after the application.” 17. Most such suggestions were delivered orally by a researcher, with few studies providing such information in writing 9,21,29–31. For pain, a somewhat larger pooled nocebo effect of the combination of conditioning with verbal suggestions (k = 21, g = 0.71, 95% CI 0.60 – 0.82, I2 = 50.71%; Figure 2A) was observed than of verbal suggestions alone (k = 12, g = 0.63, 95% CI 0.40 – 0.86, I2 = 55.59%; Figure 2B). In itch, however, conditioning with verbal suggestions yielded a smaller pooled effect on the magnitude of nocebo responses (k = 4, g = 0.26, 95% CI 0.09 – 0.43, I2 = 0%; Figure 2C) compared to a medium pooled effect of verbal suggestions alone (k = 4, g = 0.53, 95% CI 0.23 – 0.82, I2 = 53.81%; Figure 2D) on nocebo responses. Overall, nocebo responses (see Table 1 for the relevant studies) were thus associated with medium pooled effects in pain, while in itch they were associated with slightly smaller pooled effects overall. Magnitude of nocebo responses based on the type of stimulation For pain studies that used conditioning with verbal suggestions, we compared effects of different pain administration methods (k = 13 thermal, k = 7 electrical) excluding the single study using laser. Thermal

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