Fig. 2

Effect of intragastric and intraarticular metformin on pain-related behavior in the destabilization of the medial meniscus (DMM)-induced OA mice model. Pain related behavior, measured as paw withdrawal thresholds to mechanical stimulation with a circular probe (a, b) or hindlimb weight-bearing asymmetry (c, d), increased after the induction of OA in mice by DMM surgery. Paw withdrawal threshold was higher in the IGM group than that in the IGS group (a). Similar results were observed between the IAM group and the IAS group (b). In addition, decreased weight-bearing asymmetry was observed in the IGM group compared with the IGS group (c). Difference with a possible trend toward significance (p = 0.052) in paw withdrawal threshold was observed among the IAM group and the IAS group (d). Data were expressed as the mean ± 95% confidence intervals. *p < 0.05, compared between the IGS and IGM groups or between the IAS and IAM groups at single time point, by repeated measures ANOVA with Bonferroni’s post hoc test; +p < 0.05; +++p < 0.001, compared between the IGS and IGM groups or between the IAS and IAM groups by repeated measures ANOVA with Bonferroni’s post hoc test; IGS, intragastric saline administration; IAS, intraarticular saline injection; IGM, intragastric metformin administration; IAM, intraarticular metformin injection