Understanding Knee Osteoarthritis Pain: The Inflammation Connection

IN KNEE osteoarthritis, an inflammation biomarker subtype linked to higher KOOS, WOMAC, NRS, and PainDETECT scores across measures. Knee Osteoarthritis Pain Outcomes Track Inflammation Researchers explored whether patient reported pain aligns with knee osteoarthritis subtypes defined by systemic biochemical biomarkers and MRI based structural pathology. Using data from 297 participants in the IMI APPROACH study, they compared multiple commonly used pain outcomes, including KOOS, WOMAC, ICOAP, an NRS for knee pain, PainDETECT, and a pain diary. To define systemic biomarker subtypes, serum and urine markers were grouped using k means clustering into three patterns: low tissue turnover, structural damage, and systemic inflammation. Separately, MRI assessments were used to classify structural pathology subtypes as inflammatory, meniscus and cartilage damage, or subchondral bone pathology. Associations between pain outcomes and these subtypes were analyzed with multivariable regression adjusted for age, sex, and BMI. Biomarkers Show Stronger Links Than MRI Damage Patterns Across several questionnaires, the systemic inflammation subtype was associated with worse pain outcomes, including higher KOOS pain, WOMAC weight bearing pain, NRS knee pain, and PainDETECT scores (all p ≤0.042; β ≥0.12). In contrast, the low tissue turnover subtype was associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ≤0.22; β ≤−0.13). The structural damage biomarker subtype was associated with lower PainDETECT scores (p=0.046; β=−0.12), a pattern the authors interpreted as more nociceptive like pain. Among MRI defined subtypes, meniscus and cartilage damage was significantly associated with lower PainDETECT scores (p=0.005; β=−0.16). No significant associations were seen for the subchondral bone subtype or for pain diary outcomes. Why This Matters for Clinical Studies Overall, the findings suggest that pain severity on commonly used questionnaires may be more closely related to inflammatory activity than to the degree of structural pathology. The authors note that pairing pain tools with biomarker and MRI phenotyping could help refine patient selection for clinical trials and observational studies in knee osteoarthritis. Reference: Jansen MPJ et al. How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort. Osteoarthr Cartil Open. 2026;8(1):100726.