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. 2022 Feb 10;23(1):25. doi: 10.1186/s10194-022-01397-w

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© The Author(s) 2022

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Blocking S1PR1 signaling attenuated mechanical or thermal hyperalgesia caused by chronic NTG administration. A Timeline of drug administration and behavioral testing. B-C Repeated daily injection of W146 before NTG could prevented basal mechanical and thermal hyperalgesia of periorbital (B) and hindpaw (C, D). E–G post—treatment responses were assessed 2 h after NTG administration. W146 could attenuate NTG-triggered acute hyperalgesia. Two-way ANOVA and Bonferroni post hoc test analysis; *p < 0.05, **p < 0.01 and ***p < 0.001 compared with the Saline group; ^#p < 0.05, ^##p < 0.01 and ^###p < 0.001 compared with the NTG group. H-J Repeated daily injection of SEW2871 (a S1PR1 agonist) before NTG did not prevent basal hyperalgesia of periorbital (H) and hindpaw (I-J). Two-way ANOVA and Bonferroni post hoc test analysis; *p < 0.05, **p < 0.01 and ***p < 0.001 compared with the Saline group