Fig. 2: Knockdown of ATF4 decreases thermal sensitivity.
From: ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking
a–j The behaviours of ATF4 siRNA- and scrambled siRNA-injected mice were evaluated by the von Frey (a), dynamic (b), tape (c), tail clip (d), pinprick (e), Hargreaves (f), tail-flick (g), hot plate (h), evaporative cooling (i) and rotarod (j) tests. n = 12 mice per group in a–g, i. n = 12 mice in scrambled and n = 11 mice in ATF4 siRNA group in h. n = 10 mice per group in j. t22 = 4.783, P < 0.0001 in f. t22 = 5.163, P < 0.0001 in 48 °C; t22 = 5.661, P < 0.0001 in 50 °C; t22 = 10.30, P < 0.0001 in 52 °C in g. t21 = 2.357, P = 0.0282 in 52 °C; t21 = 2.804, P = 0.0106 in 55 °C in h. k, l ATF4 siRNA abated SNL-induced thermal hyperalgesia (k) but not mechanical allodynia (l). n = 12 mice per group. F(1,22) = 56.9, P < 0.0001 in day 0, P = 0.0095 in day 4, P = 0.0013 in day 7, P = 0.0009 in day 10, P = 0.0089 in day 14 in k. m, n ATF4 siRNA abated CFA-induced heat hyperalgesia (m) but not mechanical allodynia (n). n = 8 mice per group. F(1,14) = 121.6, P < 0.0001 in day 0, P = 0.0007 in day 1, P < 0.0001 in day 3, P = 0.0098 in day 5 in m. o, p Spontaneous pain: total duration (o) or number (p) of nocifensive behaviour (paw licking or flinching within 2 min) in response to intraplantar injection of vehicle, PS (2.5 nmol/paw) or CIM0216 (2.5 nmol/paw) into ATF4 siRNA and scrambled mice. n = 10 mice per group. t18 = 3.231, P = 0.0046 in PS, t18 = 3.286, P = 0.0041 in CIM0216 in o. t18 = 2.429, P = 0.0258 in PS, t18 = 3.327, P = 0.0038 in CIM0216 in p. q Spontaneous pain: total duration of nocifensive behaviour (within 5 min) in response to intrathecal injection of vehicle, PS (1.25 nmol/paw) or CIM0216 (1.25 nmol/paw) into ATF4 siRNA and scrambled mice. n = 10 mice per group. t18 = 3.281, P = 0.0042 in PS, t18 = 3.024, P = 0.0073 in CIM0216. a–j, o–q Two-tailed Independent Student’s t test; k–n Two-way ANOVA followed by Bonferroni’s multiple comparisons test. *P < 0.05, **P < 0.01, n.s. means not significant. The error bars indicate the SEMs.
