MSK1 downstream signaling contributes to inflammatory pain in the superficial spinal dorsal horn
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The nuclear kinases mitogen- and stress-activated kinase 1 and 2 (MSK1 and MSK2), through regulating transcriptional processes, are pivotal for various adaptive responses, including inflammation, learning and addiction. Transcriptional alterations in neurons and glia cells within the pain signal-processing (nociceptive) pathway, including the superficial spinal dorsal horn (SSDH), are critical for the development and persistence of inflammatory pain that results from tissue injuries and subsequent inflammatory reactions. While previous reports have indicated that MSK1 contributes to transcriptional changes in inflamed tissues, the impact of MSK1 on nociceptive processing in the SSDH are poorly understood at present. Here, we report MSK1 immunoreactivity (IR) in a group of excitatory and inhibitory neurons as well as in microglia and oligodendrocytes in the SSDH. Injecting Complete Freund’s Adjuvant into the mouse hind paw produced robust non-evoked pain-related behavior, which was significantly attenuated by global depletion of MSK1. In wild-type mice, the inflammatory pain was accompanied by transient MSK1-dependent phosphorylation of the MSK1 downstream effector histone 3 at serine 10 at one hour but not two days after the injection; still, the number of nuclei exhibiting activated MSK1 expression remained highly restricted even at 1 h post-injection. Our data indicate that MSK1 contributes to inflammatory pain via epigenetic and transcriptional alterations; however, once initiated, MSK1’s downstream effects do not require further drive from the persistent activity of the MSK1 signaling pathway in the SSDH.
Date Issued
2025-12-02
Date Acceptance
2025-12-10
Citation
International Journal of Molecular Sciences, 2025, 26 (24)
ISSN
1661-6596
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
26
Issue
24
Copyright Statement
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).
License URL
Publication Status
Published
Article Number
12177
Date Publish Online
2025-12-18