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. 2022 Mar 19;12:4767. doi: 10.1038/s41598-022-08657-4

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Time plot of cortisol during all test sessions. RS resting session. ∆ = −13%, p < 0.0001. LS learning session. ∆ = −24%, p = 0.0002. L1 time point when reaching target pain. L + 15 time point L1 plus 15 min. L + 45 time point L1 plus 45 min. OS opioid session. ∆ = −18%, p = 0.0491. O1 time point of administration of opioids in addition to target pain. O + 7 7 min after O1. O + 35 35 min after O1. Arrows point to the corresponding time points. Boxes and whiskers represent mean and SD. Spearman rank correlation between cortisol levels and VAS scores at the trial endpoint time showed no correlation between VAS scores and cortisol levels (Spearman r −0.42 (95% CI −0.74 to 0.055), p = 0.07).