Fig. 2: Histone lactylation mediates the decrease of DOCK4.
a–d The pan-lactylation (Pan Kla) levels in the DRG tissues of SNL, CFA, PTX, and LLC mice. e Changes in lactate levels in the DRG tissues of mice subjected to SNL, CFA, PTX, and LLC. n = 6 mice in control, PTX and LLC groups; n = 8 mice in SNL group; n = 7 mice in CFA group. F(4, 28) = 7.84, P = 0.011 in SNL vs. control, P = 0.0002 in CFA vs. control, P = 0.0436 in PTX vs. control, P = 0.0007 in LLC vs. control. f The schematic diagram of intrathecal (i.t.) injection of sodium lactate (NaLA) (Created in BioRender. https://BioRender.com/xs51blc). g, h The effect of intrathecal injection of sodium lactate (NaLA, 50 μM) on the expression of DOCK4 in DRG tissues. n = 3 samples per group. t4 = 4.096, P = 0.0149 in (g); t4 = 2.894, P = 0.0444 in (h). i The schematic diagram of intraperitoneal (i.p.) injection of oxamate (Created in BioRender. https://BioRender.com/xs51blc). j, k The effect of intraperitoneal injection of oxamate (300 mg/kg) on the expression of DOCK4 in DRG tissues. n = 3 samples per group. t4 = 7.543, P = 0.0017 in (j); t4 = 2.837, P = 0.047 in (k). l–o The effect of oxamate on the expression of Dock4 mRNA in DRG tissues of SNL, CFA, PTX, and LLC mice. n = 3 samples per group in l, m and o; n = 4 samples per group in (n). F(2, 6) = 12.34, P = 0.0097 in sham vs. SNL, P = 0.0156 in SNL vs. SNL + oxamate in l; F(2, 6) = 11.14, P = 0.0224 in saline vs. CFA, P = 0.0113 in CFA vs. CFA + oxamate in m; F(2, 9) = 8.226, P = 0.039 in vehicle vs. PTX, P = 0.0093 in PTX vs. PTX + oxamate in n; F(2, 6) = 15.54, P = 0.0116 in IC vs. LLC, P = 0.0048 in LLC vs. LLC + oxamate in o. p The change of H3K9la, H3K18la, H3K14la, H4K5la, H4K8la, H4K12la, and H4K16la level in DRG of mice after SNL treatment. n = 3-4 samples per group. t4 = 6.515, P = 0.0029 in H4K8la; t4 = 4.34, P = 0.0122 in H4K12la. q The change of H4K8la, H4K12la, and H4K16la level in DRG of mice after CFA treatment. n = 4 samples per group. t6 = 2.691, P = 0.036. r The change of H4K8la level in DRG of mice after PTX treatment. n = 4 mice per group. t6 = 2.75, P = 0.0333. s The change of H4K8la level in DRG of mice after LLC treatment. n = 3 samples per group. t4 = 3.071, P = 0.0372. t–w ChIP-qPCR was used to assess the impact of oxamate on the relative occupancy of H4K8la with the Dock4 promoter in the DRGs of mice subjected to SNL, CFA, PTX, and LLC. n = 3 per group. F(2, 6) = 9.186, P = 0.0334 in sham vs. SNL, P = 0.0175 in SNL vs. SNL + oxamate in (t); F(2, 6) = 9.492, P = 0.0214 in saline vs. CFA, P = 0.0219 in CFA vs. CFA + oxamate in (u); F(2, 6) = 13.41, P = 0.0089 in vehicle vs. PTX, P = 0.0111 in PTX vs. PTX + oxamate in (v); F(2, 6) = 9.727, P = 0.0125 in IC vs. LLC, P = 0.048 in LLC vs. LLC + oxamate in (w). x ChIP-qPCR was used to assess the impact of sodium lactate (NaLA) on the relative occupancy of H4K8la with the Dock4 promoter in the DRGs. n = 3 per group. t4 = 4.164, P = 0.0141. y The schematic shows that pathological pain upregulates lactic acid in the DRG, leading to increased lactylation of histone H4K8, which inhibits Dock4 gene transcription (Created in BioRender. https://BioRender.com/xs51blc). g, h, j, k, p, q, r, s, x, Two-tailed Independent Student’s t test; e, l–o, t–w, One-way ANOVA followed by Tukey’s multiple comparisons test. *P < 0.05, **P < 0.01, ***P < 0.001, n.s. means not significant. Data are presented as mean ± SEM. Complete sample size and sex is provided in the Supplementary Data. Source data are provided as a Source Data file.
