{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T02:52:09Z","timestamp":1769655129947,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KH Ren\u00e9 Koczorek Stiftung"},{"name":"intramural funds of Charit\u00e9-Universit\u00e4tsmedizin Berlin"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Corticosteroid receptor signaling in primary afferent neurons of the dorsal root ganglion (DRG) has emerged as a potential target to modulate nociception via genomic and nongenomic mechanisms shown in animal pain models. However, the expression landscape of glucocorticoid receptors (GRs) relative to mineralocorticoid receptors (MRs) in human DRG, their association with pain-related markers, and their functional relevance remain incompletely defined. We analyzed human and rat DRG by mRNA profiling and immunofluorescence confocal microscopy to assess GR\/MR expression and complemented these studies with a clinical evaluation of neuraxial corticosteroid delivery. Here, GR transcripts in human DRG were the most abundant among corticosteroid receptor-related genes examined (including MR) and were observed alongside transcripts of pain-signaling molecules. Human DRG immunofluorescence analysis revealed substantial colocalization of GR with calcitonin gene-related peptide (CGRP), a marker of nociceptive unmyelinated C-fibers and thinly myelinated A\u03b4-fibers, as well as with gial fibrillary acidic protein (GFAP), a marker of satellite glial cells (SGCs), but minimal expression in myelinated neurofilament 200 (RT-200) immunoreactive (IR) human DRG neurons. In addition, GR immunoreactivity was primarily distributed to medium-diameter neurons (40\u201365 \u00b5m). Functionally, preclinical experiments showed that GR activation and MR blockade attenuate inflammatory pain via rapid, nongenomic neuronal mechanisms that counter an intrinsic mineralocorticoid receptor-mediated pronociceptive drive. Consistently, clinical analgesia over at least 3 months after transforaminal plus caudal epidural delivery of GR agonists in chronic radicular pain supports a functional role for neuronal GR signaling within spinal cord and DRG circuits. Together, these molecular, functional, and clinical findings identify GR as a key modulator of sensory neuron excitability and pain, highlight MR as a pronociceptive counterpart, and suggest that selectively enhancing GR signaling or inhibiting MR signaling may offer a potential strategy for improving corticosteroid-based analgesic therapies.<\/jats:p>","DOI":"10.3390\/cells15030223","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:24:36Z","timestamp":1769423076000},"page":"223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human DRG Glucocorticoid Receptor Profiling Reveals Targets for Regionally Delivered Steroid Analgesia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-7422","authenticated-orcid":false,"given":"Shaaban A.","family":"Mousa","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6793-7895","authenticated-orcid":false,"given":"Elsayed Y.","family":"Metwally","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongjuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shenzhen Second People\u2019s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen 518035, China"}],"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 Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-7280","authenticated-orcid":false,"given":"Oscar Andr\u00e9s","family":"Retana Romero","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, 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 Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Benjamin Franklin, 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 Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Shaqura","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.clinbiochem.2004.11.009","article-title":"The mechanisms of differential glucocorticoid and mineralocorticoid action in the brain and peripheral tissues","volume":"38","author":"Rashid","year":"2005","journal-title":"Clin. 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