Figure 1.
Adjuvant-induced mechanical hyperalgesia throughout the 21-day experimental period.
Each data point represents the mean ± SEM of the percentage decrease of the mechanonociceptive threshold of (A) Tac1−/−, (B) Tac4−/−, (C) Tacr1−/−, (D) Tac1−/−/Tac4−/− mice compared to the initial control values (n = 9–24 mice per group; *p<0.05, **p<0.01, ***p<0.001 vs. C57Bl/6; two-way ANOVA followed by Bonferroni’s modified t-test).
Figure 2.
Adjuvant-induced oedema throughout the 21-day experimental period.
Each data point represents the mean ± SEM of the percentage increase of the paw volume of (A) Tac1−/−, (B) Tac4−/−, (C) Tacr1−/−, (D) Tac1−/−/Tac4−/− mice compared to the initial control values (n = 9–24 mice per group, two-way ANOVA followed by Bonferroni’s modified t-test).
Figure 3.
Histopathological changes of the paws on day 21.
Panel A shows a representative histopathological picture of an intact tibiotarsal joint and panel B demonstrates the joint structure of an adjuvant-treated C57Bl/6 wildtype mouse with remarkable synovial swelling, leukocyte infiltration, cartilage damage, and bone destruction. The lower panes demonstrate the joint structures of adjuvant-treated (C) Tac1−/−, (D) Tacr1−/−, (E) Tac4−/−, and (F) Tac1−/−/Tac4−/− mice, decreased inflammatory parameters can be observed in the latter two groups. Hematoxylin-eosin staining, 40x magnification (ti: tibia, ta: tarsus, s: synovium). (G) Semiquantitative histopathological scoring on the basis of inflammatory cell accumulation, synovial enlargement, cartilage destruction and bone erosion. Box plots represent the composite scores (n = 4–12 mice per group,+++p<0.001 vs. intact C57Bl/6, *p<0.05, ***p<0.001 vs. C57Bl/6 CFA-treated, Kruskal-Wallis followed by Dunn’s post test).
Figure 4.
Concentrations of the inflammatory cytokine interleukin-1β (IL-1β) in the joint homogenates on day 21.
Each bar represents the mean ± SEM of each group (n = 5–12 mice per group, *p<0.05 vs. C57Bl/6; Kruskal-Wallis followed by Dunn’s post test).
Table 1.
Summary of functional, morphological and immunological alterations in gene-deleted mouse strains compared to the C57Bl/6 WT group.