{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:34:26Z","timestamp":1769589266616,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KH Ren\u00e9 Koczorek Stiftung"},{"name":"DFG"},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin"},{"name":"Berlin Institute of Health at Charit\u00e9 (BIH)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11\u03b2-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11\u03b2-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated A\u03b4-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (&gt;70 \u00b5m). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies.<\/jats:p>","DOI":"10.3390\/cells14151142","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T10:28:09Z","timestamp":1753352889000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Components of Mineralocorticoid Receptor System in Human DRG Neurons Co-Expressing Pain-Signaling Molecules: Implications for Nociception"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-7422","authenticated-orcid":false,"given":"Shaaban A.","family":"Mousa","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsayed Y.","family":"Metwally","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5623-8400","authenticated-orcid":false,"given":"Sascha","family":"Tafelski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-6393","authenticated-orcid":false,"given":"Jan David","family":"Wandrey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"BIH Charit\u00e9 Digital Clinician Scientist Program, BIH Biomedical Innovation Academy, Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-8915","authenticated-orcid":false,"given":"J\u00f6rg","family":"Piontek","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-7680","authenticated-orcid":false,"given":"Sascha","family":"Treskatsch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-706X","authenticated-orcid":false,"given":"Michael","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Shaqura","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000124506","article-title":"Aldosterone effects on salt appetite in adrenalectomized 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