Hindpaw von Frey following CFA in systemic inducible
Pi16−/− (A-B) and
fibroblast-specific inducible Pi16−/−
(C-D). Cre-positive (Cre+) or wild-type littermate controls (WT) were
treated with vehicle (VEH) or tamoxifen (TAM) between baseline measurements 1
and 2 (days −7 and −1 relative to intraplantar CFA). (A, B)
Systemic inducible deletion of PI16 protects females from acute and prolonged
CFA-induced hypersensitivity, whereas males only show attenuation of pain up to
11–15 days post-CFA. (C, D) Inducible deletion of PI16 from
Col1a2 fibroblasts protects female (C) and male (D) mice
from prolonged CFA-induced mechanical hypersensitivity. Merged results from (C)
and (D) are depicted in panel (E). Two-way repeated-measures ANOVA,
Šidák’s multiple comparisons tests: Cre+ + TAM
vs WT + TAM: *P<0.05, **P<0.01, ***P<0.005,
****P<0.0001. Cre+ + TAM vs Cre+ + VEH:
#P<0.05, ##P<0.01, ####P<0.0001.