Fig. 2: Role of peripheral NAAA and PPAR-α signaling in initiation of hyperalgesic priming.
From: NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice
A–C IL-6-primed mice were treated on 1d-3d with ARN19702 (ARN, 30 mg-kg−1) alone or in combination with GW6471 (4 mg-kg−1; n = 8), T0070907 (1 mg-kg−1; n = 7), AM630 (3 mg-kg−1; n = 8), or an appropriate vehicle (n = 8). Effects of PGE2 in mice treated with the following: (A) ARN19702 alone (green triangles), ARN19702 plus GW6471 (open squares), or vehicle (Veh, magenta circles); (B) ARN19702 alone (green triangles), ARN19702 plus T0070907 (open squares), or vehicle (magenta circles); and (C) ARN19702 alone (green triangles), ARN19702 plus AM630 (open squares), or vehicle (magenta circles). (D, E) IL-6-primed mice were treated on 1d-3d with PEA (30 mg-kg−1; n = 8) or GW7647 (10 mg-kg−1; n = 8). Effects of PGE2 in mice treated with (D) PEA (green circles) or vehicle (magenta circles); and (E) GW7647 (green circles) or vehicle (magenta circles). F Time-course of ARN726 concentrations in plasma (green circles) and spinal cord (gray squares) after IP administration in mice (10 mg-kg−1; n = 5 per group/time point). Top, chemical structure of ARN726. Right panel, area under the curve (AUC). G–I Effect of ARN726 (10 mg-kg−1) on plasma concentrations of (G) PEA, (H) OEA, and (I) anandamide (AEA). Gray bars, baseline plasma concentrations. J–L Effect of ARN726 (10 mg-kg−1) on the spinal cord concentrations of PEA (J), OEA (K), and AEA (L). Open bars, baseline analyte concentrations. M IL-6-primed mice (n = 7-8 per group) were treated on 1d-3d with ARN726 (1-30 mg-kg−1) and the response to PGE2 was assessed on 6d. % MPE, percent of maximal possible effect. N Effects of intrathecal vehicle (magenta circles) or ARN726 (30 ng, administered on 1d and 3d) (green circles) on the response to PGE2 in IL-6 primed mice (n = 7-8 per group). Data are presented as mean ± S.E.M. and were analyzed using the two-tailed unpaired Student’s t test (F, AUC), one-way ANOVA (G–L), or two-way repeated measure ANOVA (A–F, N). Dunnett’s or Bonferroni’s post hoc test was applied as needed. P values versus vehicle or baseline/time 0 are indicated. Dotted lines indicate baseline withdrawal latency. Source data are provided as a Source Data file.
