Linking Intra-Articular Inflammatory Biomarkers with Peripheral and Central Sensitization in Late-Stage Knee Osteoarthritis Pain: A Pilot Study
Open accessAbstract
Background/Objectives: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods: A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results: The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R2 = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R2 = 0.827; p = 0.001) and relative CPM (R2 = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R2 = 0.728; p = 0.02). Conclusions: This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions.
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Rapid biomarker assays targeting inflammatory markers such as IL-1β, TNF-α, and IL-6 and indicators of cartilage degradation are being developed.
“Targeting inflammatory markers like IL-1β, TNF-α, and IL-6 as well as indicators of cartilage degradation, rapid biomarker assays—such as lateral flow tests using antibody-coated nanoparticles (yielding results in 10–20 min with nanogram-range sensitivity), microfluidic lab-on-a-chip platforms (employing colorimetric, fluorescent, or electrochemical readouts), and multiplexed biosensors with”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [135]
The Methods (§2.3.4; page unavailable) report a multiplex assay measuring IL-1β, TNF-α, IL-6, MMP-1 and MMP-7; §2.4 identifies the latter two as indicators of cartilage degeneration. The paper does not report that rapid assays are being developed or describe the cited lateral-flow, microfluidic or biosensor technologies, their turnaround times, or their sensitivity. (LLM, conf=0.85)
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- Authors
- Puts, S., Njemini, R., Bilterys, T., Lefeber, N., Scheerlinck, T., Nijs, J., Beckwée, D., & Bautmans, I.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Universitair Ziekenhuis Brussel (BE)
- Corresponding author
- Bautmans, Ivan
- ORCID
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2024-09-02
- Volume
- 13
- Issue
- 17
- Pages
- 5212
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC11395782
- OpenAlex
- W4402130580
- Cited by
- 15
- References
- 59
- Citations by year
- 2026: 10 · 2025: 5
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Research Foundation Flanders (FWO) (G040919N, SRP59, WFWG12-14, WFWG20-02, WFWG23-18)
- Research Council of Vrije Universiteit Brussel (G040919N, SRP59, WFWG12-14, WFWG20-02, WFWG23-18)
- Wetenschappelijk Fonds Willy Gepts of the UZ Brussel (G040919N, SRP59, WFWG12-14, WFWG20-02, WFWG23-18)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- knee osteoarthritis, synovial fluid, peripheral sensitization, central sensitization, chronic pain, acute inflammation, cartilage degeneration, neurotrophins, pressure pain threshold, conditioned pain modulation, temporal summation, total knee arthroplasty, CXCL9, MMP-1, MMP-7, IL-10, nerve growth factor, brain-derived neurotrophic factor
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