MSK1 Downstream Signaling Contributes to Inflammatory Pain in the Superficial Spinal Dorsal Horn

Journal article

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.

Authors: Irfan, J; Febrianto, RM; Mira D’Ercole, A; Li, N; Danke, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: International Journal of Molecular Sciences
• Volume: 26
• Issue: 24
• Pages: 12177-12177
• Article number: 12177
• Publication date: 2025-12-18
• Acceptance date: 2025-12-10
• DOI: 10.3390/ijms262412177
• EISSN: 1422-0067
• ISSN: 1661-6596
• Language: English
• Keywords: glia; nociceptive processing; spinal cord; neuron