Fig. 1: NAAA is required to induce hyperalgesic priming.
From: NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice
A Model used in the present study. In most experiments, priming was induced in mice by intraplantar administration of IL-6 and was assessed 6 days later by injecting PGE2 at the same site. Ipsilateral heat hypersensitivity (paw withdrawal latency, seconds) was measured under baseline (BL) conditions (−2d, −1d) and immediately after administration of IL-6 (0d), PGE2 (6d), or vehicle (0d and 6d). The blue bar marks the incubation period for priming. The illustration was generated, in part, with BioRender.com. B, D Self-resolving heat hypersensitivity elicited by IL-6 in mice that had received 2 h earlier (B) ARN19702 (ARN, 30 mg-kg−1; green circles; n = 8), (D) gabapentin (GBP, 50 mg-kg−1; green triangles; n = 8), or their vehicles (Veh, magenta circles; n = 8). C, E Effects of PGE2 in IL-6-primed mice treated with ARN19702 (C), gabapentin (E), or their vehicles. F, G IL-6-primed mice were treated on 1d-3d with vehicle (n = 16) or ARN19702 (30 mg-kg−1; n = 17). F Response to IL-6 before administration of vehicle (open symbols) or ARN19702 (closed symbols). G Effects of PGE2 in IL-6-primed mice that had received vehicle (magenta circles) or ARN19702 (green triangles). Right panel, area under the curve (AUC). H–J IL-6-primed mice (n = 10 per group) were treated with vehicle (magenta circles) or ARN19702 (30 mg-kg−1, filled triangles) for 2 days on 1d-2d, 3d-4d, or 5d-6d, and the response to PGE2 was assessed 3 days later. ARN19702 on (H) 1d-2d, (I) 3d-4d, and (J) 5d-6d. (K, L) Effects of (K) IL-6 (0d) and (L) PGE2 (6d) in wild-type (Wt, magenta circles, n = 10), heterozygous Naaa+/- (green triangles, n = 11), and homozygous Naaa-/- mice (green squares, n = 11). Data are presented as mean ± S.E.M. and were analyzed by two-way repeated measure ANOVA followed by Bonferroni’s multiple comparison test, when necessary. ***P < 0.001, **P < 0.01, *P < 0.05, versus baseline; ###P < 0.001, ##P < 0.01, #P < 0.05, versus vehicle or Wt. ns, non-significant. P values versus vehicle are shown, when possible. Dotted lines indicate baseline withdrawal latency. Source data are provided as a Source Data file.
