Paw withdrawal latencies to heat stimulation. Bar graphs show the results of the heat test in naïve 2, 6–9, 12–15, and ≥18 months old α-GAL deficient (Fabry ko) and wild-type (WT) male (a) and female (b) mice. Two months old male and female Fabry ko mice show shorter withdrawal latencies when compared with their WT littermates. In both genders, heat withdrawal latencies increased with aging and were longer in ≥18 months old Fabry KO mice compared to WT littermates. In (c) results of male and female naïve 2 and ≥18 months old α-GAL deficient Fabry ko and WT mice are averaged each. While young Fabry ko mice show heat hypersensitivity, old Fabry ko mice develop heat hyposensitivity with increased paw withdrawal latencies to heat stimulation when compared with their WT littermates. Fabry ko: 2 months (7 male, 17 female), 6–9 months (31 male, 35 female), 12–15 months (23 male, 22 female), ≥18 months (24 male, 44 female). WT: 2 months (6 male, 6 female), 6–9 months (35 male, 33 female), 12–15 months (34 male, 13 female), ≥18 months (25 male, 20 female). F = female; M = male; mo = months; n.s. = not significant; *p < 0.05, **p < 0.01.