Fig. 3: Loss of DOCK4 in sensory neurons enhances heat nociception.

a Diagram illustrating the injection of non-targeting (NT)-siRNA or DOCK4-siRNA into the sciatic nerve of mice, followed by behavioral and immunostaining tests conducted 2 days post-injection. b The behaviors were tested in NT-siRNA or DOCK4-siRNA injected mice by Hargreaves experiment. n = 16 mice/group. t₃₀ = 4.411, P = 0.0001. c Short-term conditional place aversion (CPA) assays pairing in dark chamber with heat (cutoff 8 s), punctate (1.0 g) and dynamic stimuli were performed in NT-siRNA and DOCK4-siRNA injected mice. d The short-term CPA scores induced by Hargreaves stimuli was assessed in NT-siRNA and DOCK4-siRNA injected mice. n = 7 mice/group. t₁₂ = 2.213, P = 0.047. e Diagram illustrating the intrathecal injection of AAV-hSyn-GFP or AAV-hSyn-Cre-GFP into Dock4^flox/flox mice, followed by behavioral and molecular biology tests conducted 21 days post-injection. f–h The behaviors were tested in AAV-GFP and AAV-Cre injected Dock4^flox/flox mice by Hargreaves, tail-flick, and hot plate experiments. n = 6 mice/group. t₁₀ = 5.439, P = 0.0003 in (f). t₁₀ = 3.303, P = 0.008 in 46 °C; t₁₀ = 3.053, P = 0.0122 in 48 °C; t₁₀ = 6.82, P = 0.000046 in 50°C in (g). t₁₀ = 4.76, P = 0.0008 in 50 °C; t₁₀ = 3.952, P = 0.0027 in 52 °C; t₁₀ = 3.379, P = 0.007 in 55°C in (h). i The CPA scores induced by Hargreaves training was assessed in AAV-GFP and AAV-Cre injected Dock4^flox/flox mice. n = 6 mice/group. t₁₀ = 8.817, P = 0.000005. j Diagram depicting the intraperitoneal injection (i.p.) of tamoxifen (TAM) into Dock4^WT (Dock4^flox/flox) and AvCreERT2; Dock4^CKO mice, followed by subsequent behavioral and molecular biology tests. k–r The behaviors were tested in Dock4^WT and AvCreERT2; Dock4^CKO mice by Hargreaves, tail-flick, and hot plate experiments with or without TAM injection. n = 8 mice in Dock4^WT group, n = 10 mice in AvCreERT2; Dock4^CKO group. t₁₈ = 8.834, P = 0.00000006 in (k); t₁₈ = 7.735, P = 0.0000008 in (l); t₁₈ = 4.432, P = 0.0003 in (m); t₁₈ = 4.089, P = 0.0007 in (n); t₁₈ = 3.913, P = 0.001 in (o); t₁₈ = 4.486, P = 0.0003 in (p); t₁₈ = 5.998, P = 0.000011 in (q); t₁₈ = 4.628, P = 0.0002 in (r). s The CPA scores induced by Hargreaves training was assessed in with or without TAM injected Dock4^WT and AvCreERT2; Dock4^CKO mice. n = 8 mice in Dock4^WT group, n = 10 mice in AvCreERT2; Dock4^CKO group. t₁₈ = 3.745, P = 0.0015. t-v The behaviors were tested in Dock4^WT and Trpv1-Cre; Dock4^CKO mice by Hargreaves, tail-flick, and hot plate experiments. n = 13 mice in Dock4^WT group, n = 12 mice in Trpv1-Cre; Dock4^CKO group. t₂₃ = 3.088, P = 0.0052 in t. t₂₃ = 2.377, P = 0.0261 in 46 °C; t₂₃ = 7.244, P = 0.0000002 in 48 °C; t₂₃ = 4.257, P = 0.0003 in 50 °C; t₂₃ = 2.875, P = 0.0086 in 52 °C in u. t₂₃ = 4.481, P = 0.0002 in 50 °C; t₂₃ = 2.171, P = 0.0405 in 52 °C; t₂₃ = 2.287, P = 0.0318 in 55 °C in v. b, d, f–i, k–v, Two-tailed Independent Student’s t 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.