Fig. 1

Intrathecal treatment with 20:4-NAPE has antinociceptive and pronociceptive effects on mechanical sensitivity based on concentration and NAPE-PLD activation. (A) The PWT to mechanical stimuli measured by the von Frey test after i.t. administration of four concentrations of 20:4-NAPE (0.2 µM, 2 µM, 20 µM, and 200 µM) was normalized to the baseline before i.t. treatment. Administration of 20:4-NAPE at a lower concentration (20 µM) increased the PWT, while a higher concentration (200 µM) decreased the PWT. (B) Pretreatment with the NAPE-PLD inhibitor LEI-401 (10 µM, i.t.) prevented the PWT increase induced by 20 µM 20:4-NAPE. (C) Pretreatment with LEI-401 (10 µM, i.t.) prevented the PWT decrease induced by 200 µM 20:4-NAPE. The data after 20 and 200 µM 20:4-NAPE application in (B,C) are the same as in (A). The statistical analysis: non-parametric Kruskal-Wallis test vs. baseline, one-way ANOVA with Dunnett’s test vs. 0.2 µM 20:4-NAPE (A); t-test vs. LEI-401 (B,C); criteria for significance ∗p < 0.05, ∗∗p < 0.01 vs. baseline before i.t. treatment, ^#p < 0.05, ^##p < 0.01, and ^###p < 0.001 vs. 0.2 µM 20:4-NAPE or LEI-401 treatment.