Fig. 1.

Intra-articular repeated administration of complete Freund’s adjuvant (CFA) induces long-term hyperalgesia and increases the satellite glial cell number. ICR mice (8–12 weeks old) were injected with 5 μl of 100% CFA (5 μg) in the right ankle joint (ipsilateral joint) four times at 1-week intervals, then underwent mechanical (a, n = 6) or thermal (b, n = 6) behavioral tests. Arrows are CFA treatments. Data are mean ± SEM of total tested mice. ***p < 0.001, 0 week vs other weeks on the ipsilateral side and ###p < 0.001, 0 week vs other weeks on the contralateral side by two-way ANOVA. PWT, paw withdrawal threshold; PWL, paw withdrawal latency. c Severity of arthritis presented as arthritis scores (percentage of maximum scores, n = 6). ***p < 0.001, 0 week vs other weeks by one-way ANOVA. d Dorsal root ganglia (DRG) were taken at 0, 1, 4, 8, and 12 weeks after CFA injection, then co-immunostained with anti-glial fibrillary acidic protein (GFAP) and anti-peripherin (PERI) antibodies. Cell images showing GFAP- (green) or PERI (red)-positive neurons. Scale bar is 50 μm. e Histograms represent the mean ± SEM percentage of PERI-positive neurons surrounded by GFAP⁺ (PERI^GFAP+) to total PERI-positive (PERI_T) neurons. *p < 0.05 by the z test