Applying evidence-based cross-disciplinary concepts helps to explain the heterogeneity in pain, function, and biological measures in individuals with knee pain with/at risk of osteoarthritis

Angela M Mickle; Jared J Tanner; Udell Holmes 3rd; Ahmed Rashid; Olivier Barolette; Brittany Addison; Nicola Sambuco; Cynthia Garvan; Song Lai; Christoph Seubert; Siegfried Schmidt; Roland Staud; Jeffrey C Edberg; David Redden; Burel R Goodin; Catherine C Price; Roger B Fillingim; Kimberly T Sibille

doi:10.1097/PR9.0000000000001225

Applying evidence-based cross-disciplinary concepts helps to explain the heterogeneity in pain, function, and biological measures in individuals with knee pain with/at risk of osteoarthritis

Pain Rep. 2024 Dec 24;10(1):e1225. doi: 10.1097/PR9.0000000000001225. eCollection 2025 Feb.

Authors

Angela M Mickle^{1

2}, Jared J Tanner³, Udell Holmes 3rd³, Ahmed Rashid¹, Olivier Barolette¹, Brittany Addison¹, Nicola Sambuco³, Cynthia Garvan⁴, Song Lai⁵, Christoph Seubert⁴, Siegfried Schmidt⁶, Roland Staud⁷, Jeffrey C Edberg⁸, David Redden⁹, Burel R Goodin¹⁰, Catherine C Price³, Roger B Fillingim^{2

11}, Kimberly T Sibille^{1

2

4}

Affiliations

¹ Department of Physical Medicine & Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USA.
² Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.
³ Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA.
⁴ Department of Anesthesiology, Division of Pain Medicine, University of Florida, Gainesville, FL, USA.
⁵ Department of Radiation Oncology & CTSI Human Imaging Core, University of Florida, Gainesville, FL, USA.
⁶ Department of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
⁷ Department of Rheumatology, College of Medicine, University of Florida, Gainesville, FL, USA.
⁸ Department of Medicine, Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰ Department of Anesthesia, Washington University, St. Louis, MO, USA.
¹¹ Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA.

Abstract

Introduction: Factors contributing to individual differences in knee osteoarthritis remain elusive. Dispositional traits and socioeconomic status are independent predictors of mental and physical health, although significant variability remains. Dispositional traits serve as the biological interface for life experiences.

Objectives: We investigate group differences based on dispositional traits and poverty status, specific to (1) pain intensity and functional limitations and (2) biological measures, a clinical composite and brain age.

Methods: Adults aged 45 to 85 years with knee pain associated with chronic musculoskeletal pain provided information on demographics, socioeconomic and psychosocial factors, pain, and physical function. Kellgren-Lawrence scores were determined from knee radiographs, the clinical composite from fasting blood draws, and brain age from MRI data.

Results: One hundred seventy-three individuals participated in the study. Of those, 117 had protective dispositional traits (81 above poverty/36 in poverty), and 56 had vulnerable dispositional traits (24 above poverty/32 in poverty). With sex, study site, Kellgren-Lawrence score, and age/or image quality as covariates, significant group differences were observed across clinical pain (P < 0.001), functional limitations (P ≤ 0.001), and brain age (P ≤ 0.002) measures. Although not significant, the clinical composite measure aligned with the other outcome measures and demonstrated the hormesis inverted U pattern.

Conclusions: Groups based on dispositional traits and socioeconomic status explain differing clinical outcomes. Consistent with the allostatic load and hormesis inverted U models, one group was in an adaptive health status, 2 groups were showing signs of developing load, and the fourth group showing signs of overload, at risk of worse health outcomes.

Keywords: Brain age; Chronic pain; Dispositional traits; Financial stress; Knee osteoarthritis.