{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:36:00Z","timestamp":1790300160244,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Ministry of Science and Higher Education","award":["1250205011431-0"],"award-info":[{"award-number":["1250205011431-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease of unknown etiolgy, characterized by erosive polyarthritis that leads to joint destruction and systemic inflammatory lesions in internal organs. Pain is a primary symptom of RA and a major contributor to psychological disturbances, which influence patients\u2019 subjective evaluation of their condition. These psychological issues may stem from disruptions in central pain regulation mechanisms, such as central sensitization (CS), which can also affect central metabolic processes. The objective was to investigate how the severity of central sensitization, measured by the Central Sensitization Inventory (CSI) questionnaire (Part 1), impacts clinical and neuropsychiatric parameters, as well as the expression of genes related to inflammation, tissue destruction, carbohydrate metabolism, and fatty acid metabolism in peripheral blood mononuclear cells (PBMCs) in patients with RA. Methods involved collecting blood samples from 59 RA patients (mean age 52.0 years). Clinical status was assessed using the DAS28 index and serum levels of CRP, ASPA, and RF. Neuropsychiatric parameters were evaluated through questionnaires measuring CS severity score (CSI), pain intensity (VAS, BPI), neuropathic pain (PainDETECT), anxiety and depression (HADS), fatigue (FSS, FACIT-F), fibromyalgia symptoms (FIRST), and pain catastrophizing. Protein expression in PBMCs was measured by ELISA, while gene expression was analyzed using quantitative real-time RT-PCR. All patients exhibited moderate to high disease activity. Participants were divided into four subgroups according to their CSI scores: subclinical (0\u201329 points), mild (30\u201339 points), moderate (40\u201349 points), and severe\/extreme (50\u2013100 points). Higher CSI scores correlated with significant increases in neuropsychiatric symptoms and a notable decrease in vitality. However, clinical parameters showed no significant differences among the subgroups. Gene expression analysis revealed upregulation of genes involved in the pentose phosphate pathway (G6PD), antioxidant defense (SOD1), fatty acid metabolism (FASN, CPT1B), apoptosis (CASP3), and tissue destruction and hypernociception (MMP-9) compared to healthy controls. The pro-inflammatory cytokine IL-1\u03b2 expression was comparable to controls, while TNF\u03b1 expression was elevated only in patients with severe\/extreme CS scores. These findings suggest that CS-related disturbances may contribute to increased disease severity in RA, even in patients receiving active antirheumatic treatment. At the cellular level, disease severity appears linked to dysregulated expression of genes governing central metabolic processes, despite low expression of pro-inflammatory cytokine genes.<\/jats:p>","DOI":"10.3390\/ijms27062872","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"2872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disturbances in Central Sensitization Are Associated with Disease Severity and Alterations in Gene Expression Measured in the Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-2349","authenticated-orcid":false,"given":"Elena","family":"Tchetina","sequence":"first","affiliation":[{"name":"Immunology and Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Potapova","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology of Pain and Polymorphism of Rheumatic Diseases, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3026-069X","authenticated-orcid":false,"given":"Angele","family":"Vienozinskaite","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-0869","authenticated-orcid":false,"given":"Svetlana","family":"Glukhova","sequence":"additional","affiliation":[{"name":"Statistics Department, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-1157","authenticated-orcid":false,"given":"Maria","family":"Cherkasova","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Filatova","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology of Pain and Polymorphism of Rheumatic Diseases, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Karateev","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology of Pain and Polymorphism of Rheumatic Diseases, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr","family":"Lila","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Kashirskoe Shosse 34A, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.medcli.2023.07.014","article-title":"Rheumatoid arthritis","volume":"161","year":"2023","journal-title":"Med. 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