Figure 5.

miR-146a elicits scratching behavior, which requires TRPV1, but not TRPA1, in sensory neurons. (A) miR-146a induced dose-dependent scratching behavior, but scramble control did not cause significant scratching behavior. i.d., intradermal. *P < .05 and ***P < .001 vs normal saline (NS) (n = 4–5 mice/group). (B) The mouse cheek model demonstrated that miR-146a elicited robust scratching (itch) but not wiping response (pain). ***P < .001 vs NS (n = 4–5 mice/group). (C) Elimination of TRPV1-expressing spinal nerve terminals using intrathecal (i.t.) injection of resiniferatoxin (RTX, 200 ng/5 μL) significantly reduced miR-146a– or LPC-induced itch. *P < .05 and **P < .01 vs vehicle (Veh, 2% ethanol ⁺ 2% Tween 80) (n = 4–5 mice/group except n = 11 for vehicle ⁺ LPC). (D and E) miR-146a– and LPC-induced itch were significantly attenuated by intraperitoneal (i.p.) (2 mg/kg) or i.t. (30 μg) injection of the TRPV1 inhibitor SB366791, or in Trpv1 KO. *P < .05 and **P < .01 vs WT (n = 4–5 mice/group for D and n = 6–11 mice/group for E). Itch induced by (F) miR-146a (n = 4–5 mice/group) and (G) LPC (n = 5–11 mice/group) were not significantly altered by i.p. (30 mg/kg) or i.t. (30 μg) injection of the TRPA1-inhibitor HC030031, or in Trpa1 KO. One-way analysis of variance with Tukey’s post hoc test was used for A and D–G, 2-tailed t test for B and C. The error bars show the standard error of the mean.