Fig. 6: IL-33-CCL2-induced pain hypersensitivity is mediated by the up-regulation of TRP channels in the hindpaw and enhancement of c-fiber- evoked LTP in the spinal cord.
From: IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8
(A–C) Gene expression of TRPV1 (A), TRPV4 (B) and TRPM8 (C) in the hindpaw skin in ST2−/− mice at 4 h after IL-33 injection (n = 5-7 mice). D Colocalization of TRPV1(upper panel) and TRPM8(lower panel) with PGP9.5 in the hindpaw (n = 3 mice, scale bar: 100 μm). Blocking TRPV1 with AMG9810 attenuated IL-33-induced mechanical (E) and thermal hypersensitivity (F) (n = 6 mice). G Blocking TRPV1 with capsazepine (CPZ) attenuated IL-33-induced thermal hypersensitivity (n = 6 mice). H Blocking TRPM8 with AMG2850 attenuated IL-33-induced cold allodynia (n = 6). I Expression of TRPV1 in DRGs (n = 3 mice, scale bar: 100 μm). J Quantification of (I), TRPV1-postive number in DRGs(n = 3 mice). K Colocalization of CCR2 with PGP9.5 in the hindpaw (n = 3 mice, scale bar: 100 μm). Intraplantar injection of CCL2 induces mechanical (L) and thermal hypersensitivity (M) (n = 6 mice). N Representative LTP traces show c-fiber-evoked field potentials in the dorsal horn of spinal cord in various inflammatory pain models. O Quantification of (N) (n = 5 rats). P Representative LTP traces show c-fiber-evoked field potentials in the dorsal horn of spinal cord by pretreatment with AMG9810 and AMG2850 in CCL2-induced model (n = 3 rats). Data are presented as mean ± SEM. *p < 0.01, **p < 0.01, ****p < 0.0001, #p < 0.05, ##p < 0.01, ###p < 0.001, ####p < 0.0001, $p < 0.05, $$p < 0.01, $$$$p < 0.0001. #g represents WT vs ST2−/− or vehicle vs drug treatment and $represents PBS+veh vs IL-33+drug treatment (0.5 μg CPZ in (G) or AMG2850 in (H)). One-way ANOVA with Bonferroni’s post-hoc test for (A–C, E, F), unpaired t-test for (J, O, P), Repeated measures for two-way ANOVA with Bonferroni’s post-hoc test for (G, H, L, M).
