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. 2017 Sep 29;7:12452. doi: 10.1038/s41598-017-12717-5

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Acetaminophen and 4-aminophenol reduce nociceptive behavior evoked by i.pl. injection of RTX in naive mice but not in mice i.c.v.-administered RTX. Time course of licking/biting behavior evoked by i.pl. injection of RTX (1 ng to the hindpaw, arrowheads in a, c, e, g) and total time spent licking/biting during the first 10 minutes of the tests are shown. Naive, untreated mice were used in a, b, e and f. In c, d, g and h, mice were pretreated with RTX (100 ng, i.c.v.) or vehicle one week before the tests. Acetaminophen and 4-aminophenol hydrochloride were i.p.-administered 20 min before i.pl. injection. All data represent the mean ± SEM. The number of mice in each group is shown in parentheses. Non-parametric multiple comparisons with Bonferroni correction following the Kruskal-Wallis test were used for b and f (two comparisons in three groups, *P < 0.05 vs. Vehicle group). The Mann-Whitney U-test was used for d and h (*P < 0.05 vs. Vehicle-i.c.v. group). PG, propyleneglycol; AcAP, acetaminophen; 4-AP; 4-aminophenol hydrochloride; n.s., not significant; i.pl., intraplantar injection.