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. 2022 May 25;13(5):500. doi: 10.1038/s41419-022-04964-w

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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 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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Fig. 6 — Time course of paw withdrawal responses in mice displaying paclitaxel (PAC)-induced cold (A) (two-way ANOVA, effect of time × treatment F (10,285) = 21.69; p < 0.0001 followed by Bonferroni’s multiple comparisons test) and mechanical (B) (two-way ANOVA, effect of time × treatment F (10,285) = 17.63; p < 0.0001 followed by Bonferroni’s multiple comparisons test) allodynia treated or not with a C5aR1 inhibitor, DF3966A (30 mg/kg). DF3966A was orally administered every 12 h for 14 days during the induction phase of CIPN. Cold and mechanical allodynia were evaluated 3 h after DF3966A treatment on days 1, 3, 5, 7, 10 and 14. (C) Real time-PCR analysis of C5aR1 (one-way ANOVA, effect of treatment F (2,27) = 6.381; p = 0.0054 followed by Bonferroni’s multiple comparisons test) and TNF-α (one-way ANOVA, effect of treatment F (2,27) = 14.79; p < 0.0001 followed by Bonferroni’s multiple comparisons test) expression levels in the spinal cord, and of (D) C5aR1 (one-way ANOVA, effect of treatment F (2,27) = 3.480; p = 0.0452 followed by Bonferroni’s multiple comparisons test), TRPV1 (one-way ANOVA, effect of treatment F (2,27) = 6.349; p = 0.0055 followed by Bonferroni’s multiple comparisons test), TRPV4 (one-way ANOVA, effect of treatment F (2,27) = 4.050; p = 0.0290 followed by Bonferroni’s multiple comparisons test), IL-1β (one-way ANOVA, effect of treatment F (2,27) = 13.81; p < 0.0001 followed by Bonferroni’s multiple comparisons test) and IL-6 (one-way ANOVA, effect of treatment F (2,27) = 1.898; p = 0.1694 followed by Bonferroni’s multiple comparisons test) in paw samples collected at day 15 after the first paclitaxel administration. ***P < 0.0005 and *P < 0.05 vs respective sham group; ⁺⁺⁺P < 0.0005; ⁺⁺P < 0.005 and ⁺P < 0.05 vs paclitaxel. Data are expressed as mean ± SEM; n = 10 per group.