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. 2017 Aug 21;7:8870. doi: 10.1038/s41598-017-09200-6

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© The Author(s) 2017

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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Arthritic ICR mice show long-lasting inflammation and bilateral mechanical hyperalgesia. Mice were injected with 5 μg complete Freund’s adjuvant (CFA) in the right ankle joint (ipsilateral joint) once a week for 4 weeks. The joint swelling in 0, 4, 8, 12 weeks was photographed (A). Scale bar, 5 mm. (B) Severity of arthritis presented as arthritis scores. Arrows are CFA treatments. ***p < 0.001, compared with 0 week by one-way ANOVA. (C) Diameters of ipsilateral (ipsi) and contralateral (contra) ankle joints. ***p < 0.001, ipsilateral vs contralateral by two-way ANOVA. (D) Threshold of paw withdrawal (PWT) to mechanical stimuli measured at weekly intervals in CFA-injected or uninjected mice (control). Data are mean ± SEM of n = 6 mice with CFA injection and n = 3~8 mice without injection. ***p < 0.001, ipsilateral vs contralateral; ^###p < 0.001, CFA-injected vs uninjected by two-way ANOVA. (E) Serum level of TNFα. ^#p < 0.05, compared with 0 weeks by nonparametric Mann-Whitney U test. (F) Serum level of IL-6. *p < 0.05, compared with 0 weeks by nonparametric Mann-Whitney U test. (G) pH value in synovial fluid in arthritic mice. Data are mean ± SEM. *p < 0.05, **p < 0.01, compared with 0 weeks by one-way ANOVA. qRT-PCR analysis of gene expression in ipsilateral DRG (H) and in contralateral DRG (I). Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, compared with 0 weeks by one-way ANOVA.