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. 2020 Jul 7;10:11130. doi: 10.1038/s41598-020-67974-8

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© The Author(s) 2020

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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KEGG enrichment bubble chart (a) shows the comparison between the low dose tramadol group and the control group; (b) shows the comparison between the high dose tramadol group and the control group; (c) shows the comparison between the high dose tramadol group and the low dose tramadol group. The abscissa in Fig. 5 is the ratio of the number of differentially changed metabolites in the corresponding pathway to the total number of identified metabolites. The higher the ratio, the higher the concentration of differentially changed metabolites in the pathway. The color of the dot represents the P-value of the hypergeometric test. The smaller the P value, the greater the reliability and the more statistically significant the test. The size of the dot represents the number of differentially changed metabolites in the corresponding pathway. A larger point size represents a greater number of differentially changed metabolites in the pathway.