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. 2021 Jul 5;18:150. doi: 10.1186/s12974-021-02198-9

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© The Author(s) 2021

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. 4 — Red nucleus IL-33 facilitates the early development of mononeuropathic pain by activating ERK signaling pathway. A Western blotting showed that red nucleus p-ERK was increased at 1 week post-SNI, intrarubral injection of anti-IL-33 antibody inhibited the upregulation of p-ERK (n = 6 per group, F = 12.666, P < 0.001). B Western blotting indicated that intrarubral injection of IL-33 promoted the protein expression of p-ERK in naive rats (n = 6 per group, F = 14.495, P < 0.001). C Immunohistochemistry showed that p-ERK was upregulated in the RN of SNI rats (F = 69.719, P < 0.001) and IL-33-induced hypersensitivity rats (F = 40.034, P < 0.001) (n = 4 per group). D Intrarubral administration of ERK inhibitor PD98059 at 1 week post-injury attenuated SNI-induced mononeuropathic pain compared to DMSO control (n = 5-6 per group, F = 102.911, P < 0.001). E Intrarubral pre-injection of PD98059, 30 min before IL-33 administration, relieved IL-33-evoked mechanical hypersensitivity compared to DMSO control (n = 5–6 per group, F = 35.306, P = 0.002). *P < 0.05, **P < 0.01, and ***P < 0.001. Scale bars = 50 μm