Figure 3. Evaluation of mechanical hypersensitivity across age.

Formalin-induced mechanical hypersensitivity was evaluated 60, 120, and 180 min after right paw formalin injection. (a) Hypersensitivity development in the non-injected left paw varied with age (Two-way RM ANOVA, effect of age p=0.0464, time × age interaction p=0.0032; n=8–10). Old mice quickly developed robust hypersensitivity that was maintained for 180 min (Bonferroni post-test for 22 mo, baseline vs. 60 min ***p<0.001, baseline vs. 120 or 180 min **p<0.01). This old-aged specific hypersensitivity was significantly different than the responses of middle-aged mice 60′ and 180′ following injection (Bonferroni post-test at 60′ 12 vs. 22 mo *p<0.05, at 180′ 12 vs. 22 mo *p<0.05). Young mice also had significantly lower withdrawal thresholds 180′ following injection when compared to middle-aged mice, however these thresholds did not differ significantly from baseline thresholds for this age group (Bonferroni post-test at 180′ 2 vs. 12 mo **p<0.01, for 2 mo baseline vs. 60, 120, or 180 p>0.05). (b) Hypersensitivity development in the injected right paw varied between the ages across time (Two-way RM ANOVA, effect of time p<0.0001, time × age interaction p=0.0309; n=8–10). Both middle-aged and old mice exhibited significant hypersensitivity 60, 120, and 180 min following injection (Bonferroni post-test for 12 mo, baseline vs. 60 or 120 min ***p<0.001, baseline vs. 180 min ****p<0.0001; Bonferroni post-test for 22 mo baseline vs. 60, 120, or 180 min ****p<0.0001).