Exploring Different Models of Pain Phenotypes and Their Association with Pain Worsening in People with Early Knee Osteoarthritis: The MOST Cohort Study

Objective: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years.

Design: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening.

Results: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening.

Conclusion: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.