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. 2021 Jun 2;37(9):1289–1302. doi: 10.1007/s12264-021-00709-5

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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/.

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Fig. 6 — Schematic showing how GDF-15 modulates peripheral nociceptive information. GDF-15 inhibits Nav1.8 on nociceptors by membrane ALK2 and downstream intracellular signals, such as PKA and ERK, leading to a reduction in the excitability of DRG neurons and pain relief.