Fig. 3.
Effect of intrathecal suppressor of variegation 3-9 homolog 1 (SUV39H1 [SUV]) inhibitor chaetocin on spinal nerve ligation (SNL)–induced nociceptive hypersensitivity. (A–E). Pretreatment of chaetocin dose-dependently blocked the decreases in paw withdrawal thresholds (PWTs) to mechanical stimulation (A) and in paw withdrawal latencies (PWLs) to thermal (B) or cold (C) stimulation on the ipsilateral (Ipsi) side and had no effects on basal paw withdrawal responses to mechanical (D) and thermal (E) stimuli on the contralateral (Cont) side. n = 5 rats/group. Two-way ANOVA (effect vs. group × time interaction) followed by post hoc Tukey test, Fgroup (12, 99) = 16.3 (A), Fgroup (12, 99) = 28.8 (B), Fgroup (12, 99) = 158.7 (C), Fgroup (12, 99) = 0.0004 (D), and Fgroup (12, 99) = 0.6 (E). *P < 0.05 or **P < 0.01 versus the corresponding time point in the vehicle (Veh) plus SNL group. (F–H) Posttreatment of chaetocin at 2 μg attenuated the decreases in paw withdrawal thresholds to mechanical stimulation (F) and in paw withdrawal latencies to thermal (G) or cold (H) stimulation on day 9 post-SNL on the Ipsi side. Behavioral tests were carried out 1 day before surgery, before drug injection on day 7 postsurgery, and on day 9 postsurgery. n = 5 rats/group. Two-way ANOVA (effect vs. group × time interaction) followed by post hoc Tukey test, Fgroup (6, 59) = 205.4 (F), Fgroup (6, 59) = 87.9 (G), and Fgroup (2, 29) = 17.5 (H). **P < 0.01 versus the corresponding time point in the Veh plus SNL group. (I, J) Pretreatment of chaetocin at 2 μg blocked the SNL-induced spontaneous ongoing nociceptive responses. n = 5 rats/group, *P < 0.05 or **P < 0.01 versus the corresponding preconditioning (Pre; I) or the Veh plus SNL group (J) by two-tailed paired Student’s t test. (K) Intrathecal chaetocin at 2 μg did not affect the expression of G9a’s two protein isoforms, SUV protein, and dimethylation of Lys9 on histone H3 (H3K9me2) in the DRGs of sham rats. L = long isoform; Post = postconditioning; S = short isoform. n = 3 repeats (6 rats)/group.