Type I IFNs induce mechanical nociceptive hypersensitivity responses via a peripheral action in male and female mice. A–D, In male mice, intraplantar (i.pl.) administration of IFN-α (300 U/25 μl) or IFN-β (300 U/25 μl) increased paw mechanical hypersensitivity (g) to von Frey stimulation (A, B) with no significant changes in paw withdrawal latency (s) to thermal stimulation (C, D). n = 9 (vehicle groups) and n = 12 (IFN groups) in A and B. n = 6 (vehicle groups) and n = 12 (IFN groups) in C and D. E–H, In female mice, intraplantar administration of IFN-α (300 U/25 μl) and IFN-β (300 U/25 μl) increased paw mechanical sensitivity to von Frey stimulation (E, F) with no significant changes in paw withdrawal latency (s) to thermal stimulation (G, H). n = 6 per group. I–L, When versus female, no significant sex differences in the development of mechanical hypersensitivity (I, J) or the presence of thermal sensitivity (K, L) were observed between groups following either IFN-α (300 U/25 μl) or IFN-β (300 U/25 μl) intraplantar administration. Data are presented as mean±SEM. Group differences were assessed using two-way ANOVA for A, B, and E, F, followed by Bonferroni's multiple-comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.