Fig. 6

Spinal inhibition of cathepsin S (CatS) in the early phase of CIA reduced mechanical hypersensitivity, microgliosis and the increased levels of pro-inflammatory cyto(chemo)kines in CSF, without affecting paw swelling. Intrathecal (i.t.) administration of the CatS inhibitor (LHVS, 30 nmol/day) from 1 day before until day 13 post-immunization significantly prevented mechanical hypersensitivity in CIA rats (a) and did not modify the clinical score (b) or paw swelling (c). LHVS reduced spinal microgliosis (Iba-1/p-p38 (d) and the increased levels of fractalkine (e) and IL-1β (f) associated with CIA. Values are the mean ± SEM of 10 rats/group (a–c) and 4–6 rats/group (d–f). ***p < 0.001, **p < 0.01, *p < 0.05 compared to vehicle group; #p < 0.05 compared to control group (a–c two-way RM ANOVA post hoc Tukey’s test; d t test; e, f one-way ANOVA post hoc Tukey’s test)