Examining Pain Phenotyping and the Role of Adipose Tissue in the Early Stage and Across the Disease Course of Knee Osteoarthritis

Abstract

Phenotyping in the early stages of knee osteoarthritis (OA) based on pain mechanisms may help to predict individualized prognosis and develop subgroup-specific treatments towards preventing symptomatic worsening. However, no phenotyping studies have been conducted in the early stages of OA, and how or if these phenotypes change over time is not known. Also, adipose tissue has been associated with systemic inflammation that can contribute to pain. To better understand different phenotypes, their association with pain worsening, their stability, and the role of adiposity in knee OA we conducted this thesis spanning three studies. In the first study, we identified different models of phenotypes based on pain-related (e.g. measures of pain sensitization and psychological factors) and pain plus disease-related (e.g. comorbidities, muscle strength) variables in early-stage knee OA. We found that none of the derived phenotypes were associated with pain worsening at two-year follow-up. In the second study, we identified different pain phenotypes using multidimensional pain characteristics in those with knee pain and at risk of knee OA, and these characteristics remained stable throughout the 7-year follow-up. The phenotypes differed in the response to pain measures (study 1 and 2), muscle strength, comorbidities, and gait features (study 1). In the third study, we identified that adiposity was not significantly associated with pain intensity and synovitis in people with knee OA and that markers of systemic immune inflammation do not have a moderating effect on this association when adjusted for confounding variables. Together, these results have implications for classifying patients in the early stages of the disease, explaining the course of different pain phenotypes before disease onset, and suggests a conflicting role of adipose tissue in OA pain/synovitis. In addition, our results guide further research towards external validation of phenotypes and determining the causal relationships between adiposity and symptoms in knee OA.