Transcription factor Sp4 is required for hyperalgesic state persistence
Fig 6
Oxaliplatin failed to induce persistent cold or mechanical hypersensitivity in Sp4+/- mice.
(A) Sp4+/- mice injected with oxaliplatin (OX) (3mg/kg ip) on day 0, induced a decrease in 4°C cold plate withdrawal latency at 24 hours in Sp4+/- and wt. mice. Beginning at 48 hours (p< 0.005) OX-injected Sp4+/- latencies differed from OX-injected wt. mice at 72 hours and 6 days (p<0.01), 10 days (p<0.05) and 14 days (** p<0.001) with Sp4+/- OX latency values indistinguishable from Veh.–injected Sp4+/-controls at 14 days (n = 6 /group). (B) Cold plate testing at 10°C with differences between Sp4+/- OX and wt. OX at 72 hours (*** p<0.0001) and 6 days (* p<0.05). Sp4+/- OX and Sp4+/- Veh. did not significantly differ at 72 hours, 6 days,10 days and 14 days (N = 6 /group). (C) Mechanical threshold testing of Sp4+/- mice injected with OX (3mg/kg ip) on day 0, induced a decrease in mechanical threshold within 24 hours in both Sp4+/- and wt. mice. Beginning at 72 hours (p<0.05), Sp4+/- OX induced mechanical allodynia progressively reversed at 6 days (p<0.005), 10 days, 14 days and 21 days (*** p<0.0001) approaching Veh—injected control values by 14–21 days. wt. OX mice showed mechanical allodynia days 1–21 (n = 6). Two-way RM ANOVA, with Bonferroni’s test. (D) Sp4+/- DRG expressed a reduction in TRPA1 and TRPM8 mRNA levels as compared to wt. DRG. (E) No change in ASIC3, TRPV4, Piezo1, Piezo2, TREK-1 or TMEM150c mRNA expression was detected in Sp4+/- as compared to wt. DRG (* p< 0.05 n = 3; ** p<0.005 n = 6; triplicate samples, two-tailed unpaired t-test. Bars = +/- SEM. Prism, GraphPad).