221: Fatigue and Central Pain Processing in Knee OA Independent of Pain (A2CPS)

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic postsurgical pain, Assessment and Measurement of Pain/Nociception, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia)

Background and Aims: Knee osteoarthritis (OA) involves both peripheral pathology and altered central nervous system (CNS) pain processing. Approximately 50% of individuals with knee OA report clinically meaningful fatigue. In musculoskeletal conditions, fatigue has been associated with heightened CNS signal processing independent of pain presence. These observations suggest fatigue may share underlying central mechanisms with pain. However, these relationships have not been rigorously examined in knee OA. We aimed to determine whether self-reported fatigue is independently associated with multiple markers of central pain processing: quantitative sensory testing (QST), multisensory sensitivity (MSS), and widespread pain using Acute to Chronic Pain Signatures (A2CPS) baseline data.

Methods: We analyzed cross-sectional baseline data from the knee cohort of the A2CPS study (Data Release v2.0). Fatigue (PROMIS T-score) was the primary outcome. Predictors included QST: pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM), MSS, and widespread pain (Michigan Body Map). Separate linear regression models were conducted for each predictor. All models were adjusted for age, sex, body mass index (BMI), education, and worst pain intensity (Brief Pain Inventory) to examine associations independent of pain severity. Statistical significance was set at p < 0.01 to account for multiple comparisons.

Results: Among 1,045 participants with complete PROMIS fatigue data (60.3% female), fatigue was associated with select central pain markers. After adjusting for age, sex, education, BMI, and pain intensity, fatigue was higher in moderate (β = 3.23, p < .0001) and high MSS (β = 7.05, p < .0001) groups versus no MSS. Fatigue was also elevated in those with widespread pain (≥5 pain areas; β = 5.00, p < .0001) but not moderate pain spread (p = .18) versus isolated pain. QST showed limited associations; TS was related to fatigue (β = 0.47, p = .002), whereas PPTs and CPM were not (p > 0.01).

Conclusions: These findings indicate that fatigue is selectively coupled to specific markers of central pain processing rather than reflecting global central dysfunction, partially supporting our hypothesis. Importantly, associations persisted after accounting for pain intensity, suggesting fatigue captures central mechanisms not fully explained by pain severity alone. Given the frequent co-occurrence of pain and fatigue in knee OA, delineating these relationships may advance understanding of fatigue pathophysiology and its shared central processes with pain. Improved characterization of these mechanisms may support more targeted strategies to address fatigue within chronic musculoskeletal conditions.

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Presenting Author: Laura Frey-Law
Submitting Author: Laura Frey Law

Senior Author: Laura Frey-Law

IASP 2026 Global Year theme of Neuropathic Pain: No

• Adam Janowski: PhD, PT - University of Iowa
• Ezgi Gillette: PhD - University of Iowa
• Giovanni Berardi: PhD, PT - University of Iowa
• Kathleen Sluka: PhD, PT - University of Iowa
• Dana Dailey: PhD, PT - University of Iowa
• Carol Vance: PhD, PT - University of Iowa
• Steve Harte: PhD - University of Michigan
• Briha Ansari: PhD - John Hopkins University
• A2CPS Consortium - multiple