Fig. 4: Blocking CCR2 attenuates IL-33-induced and CFA-induced thermal hyperalgesia in male mice.
From: IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8
Pretreatment of CCR2 antagonist (INCB3344) does not affect mechanical allodynia (A) but reduces thermal hypersensitivity (B) in IL-33-induced pain (n = 6). C Gene expression of CCL2 was partially reversed in the hindpaw of INCB3344-treated mice at 4 h after IL-33 application (n = 6 mice). D Gene expression of CCL2 in the hindpaw in ST2−/− mice at 4 h after IL-33 application (n = 6 mice). Post-treatment of INCB3344 does not affect mechanical allodynia (E) but reduces thermal hyperalgesia (F) at day 3 after CFA injection (n = 6 mice). G Protein levels of CCL2 were down-regulated in the hindpaw in ST2−/− mice at day3 in the CFA model. H Quantification of (G) (n = 4 mice). I Gene expression of CCL2 increased in the synovia of OA patients (n = 6 patients). J Gene expression of IL-33 has a trend to increase in the synovia of OA patients (n = 6 patients). K Positive correlation between the gene expression of IL-33 and gene expression of CCL2 in the synovia of OA patients (n = 6 patients). Data are presented as mean ± SEM. *p < 0.01, **p < 0.01, ***p < 0.001, ###p < 0.001. *represents PBS vs IL-33 or CFA in WT mice and #represents vehicle vs treatment or WT vs ST2−/− group in A-Fand H. Repeated measures for the two-way ANOVA with Bonferroni’s post-hoc test for (A–B), One-way ANOVA with Bonferroni’s post hoc test for (C–F, H), unpaired t-test for (I–J).
