{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:36:19Z","timestamp":1768214179202,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indonesian Endowment Fund PhD studentship"},{"name":"British Journal of Anaesthesia\/Royal College of Anaesthetists Project Grant"},{"name":"Ministry of Defence, The General Directorate of Health Services, Academic Affair, Saudi Arabia"},{"DOI":"10.13039\/501100018818","name":"Austrian Science Fund FWF","doi-asserted-by":"publisher","award":["I-050870"],"award-info":[{"award-number":["I-050870"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research, Development and Innovation Office, Hungary","award":["ANN 136027"],"award-info":[{"award-number":["ANN 136027"]}]},{"name":"Conselleria de Educaci\u00f3n, Cultura, Universidades y Empleo","award":["CIGE\/2024\/73"],"award-info":[{"award-number":["CIGE\/2024\/73"]}]},{"name":"Spanish Ministry of Science, Innovation and Universities","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}]},{"name":"European Union \u201cNextGenerationEU\u201d\/PRTR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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\u2019s downstream effects do not require further drive from the persistent activity of the MSK1 signaling pathway in the SSDH.<\/jats:p>","DOI":"10.3390\/ijms262412177","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:45:07Z","timestamp":1766065507000},"page":"12177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MSK1 Downstream Signaling Contributes to Inflammatory Pain in the Superficial Spinal Dorsal Horn"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1036-488X","authenticated-orcid":false,"given":"Jahanzaib","family":"Irfan","sequence":"first","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rizki Muhammad","family":"Febrianto","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelina","family":"Mira D\u2019Ercole","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0016-2302","authenticated-orcid":false,"given":"Nicole","family":"Li","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya","family":"Danke","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Chen","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deemah","family":"Aldossary","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle Y.","family":"Meng","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"La Montanara","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"},{"name":"Division of Neuroscience, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-9690","authenticated-orcid":false,"given":"Jose Vicente","family":"Torres-Perez","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Functional Biology and Physical Anthropology, Faculty of Biological Sciences, University of Valencia, C\/Dr. Moliner 50, 46100 Burjassot, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0183-7298","authenticated-orcid":false,"given":"David","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2892-6086","authenticated-orcid":false,"given":"Rosalie","family":"Li","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krisztina","family":"Deak-Pocsai","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, 98 Nagyerdei krt, 4012 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Segelcke","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Pradier","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther Miriam","family":"Pogatzki-Zahn","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-5399","authenticated-orcid":false,"given":"Simone Di","family":"Giovanni","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8921-7470","authenticated-orcid":false,"given":"Michaela","family":"Kress","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istvan","family":"Nagy","sequence":"additional","affiliation":[{"name":"Nociception Group, APMIC, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"},{"name":"Department of Physiology, University of Debrecen, 98 Nagyerdei krt, 4012 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41577-019-0147-2","article-title":"Pain and immunity: Implications for host defence","volume":"19","author":"Baral","year":"2019","journal-title":"Nat. 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