Novel pain phenotypes identified in patients with early-stage knee osteoarthritis

27/08/2024

Osteoarthritis (OA) is a widespread condition, with the knee being the most frequently affected joint. The pain mechanisms in knee OA (KOA) are complex and vary greatly between individuals, making it a priority to develop personalized treatment approaches. Developing tailored treatment strategies that use phenotyping to target specific pain mechanisms is essential, particularly in the early stages of the disease where preventing pain progression can lessen the long-term burden. Identifying pain phenotypes may offer a cost-effective way to understand the relationships between these phenotypes and pain progression over time. A recently published study aims to fill the current gaps in KOA phenotyping literature by examining different phenotype models and their connection to pain worsening in individuals with early-stage KOA.

Key messages

This study identified pain phenotypes in early-stage KOA, useful for targeted treatments to prevent pain progression.
There was no significant association between the established pain phenotypes and pain worsening over two years, suggesting other factors influence pain progression in early-stage KOA.
Measures of nervous system sensitivity and psychosocial variables were valuable for phenotyping, in addition gait characteristics, quadriceps strength and comorbidities may play important roles too.

Study information

Details of the study

““Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study ”(1)

Objectives

Determine phenotypes by two modelling strategies in early-stage KOA patients.
Establish patient characteristics and identify sex differences related to those phenotypes.
Study if there is a longitudinal association between pain phenotypes and pain worsening at two-year follow-up.

Methods

This study used data from the Multicenter Osteoarthritis (MOST) study to identify two phenotype models:

Model A (pain variables) included pressure pain thresholds (PPT), temporal summation (TS), conditioned pain modulation (CPM), pain catastrophizing, sleep quality, depression, and widespread pain (WSP).
Model B (pain plus disease-related variables) added gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging (MRI) features to model A variables.

Participants included those from the original cohort at the 12-year follow-up and baseline data from a new cohort added at that same time point. Early-stage KOA was defined by pain intensity ≤3/10 in the past 30-days, Kellgren-Lawrence (KL) grade ≤2, intermittent pain frequency ‘none to sometimes,’ and no constant pain. Only patients with complete data at the 14-year follow-up were included. Patients with positive peripheral neuropathy were excluded. One knee was randomly selected in individuals with bilateral KOA.

Pain phenotypes were created using Latent Class Analysis (LCA). The number of classes in each model was established using fit statistics. Each class had at least 10% of the total population. Pain worsening was defined by intermittent pain frequency ‘often or very often,’ any constant pain by the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale, and a pain VAS increase of ≥2 at the 2-year follow-up compared to baseline.

Main results

750 patients were included in model A and 333 in model B. 3-class solutions were chosen for model A and 4-class solutions for model B. WSP, measures of nervous system sensitivity and depression showed dominancy in model A most “severe” phenotype, whereas in model B gait characteristics, quadriceps strength and comorbidities are dominant features added to model A’s phenotype. Model B fitted slightly better than model A.

This study could not find any significant association between the pain phenotype classes in each model and KOA pain worsening after two years. Measures of nervous system sensitivity and psychosocial variables were important characteristics in both models. Gait variables, quadriceps strength and comorbidities contributed to the classes in model B. MRI features do not especially contribute to early-stage KOA phenotypes, except for meniscal extrusion. No significant differences were found between single classes or models to increase the risk of pain worsening.

Conclusion

This study confirms that different phenotypes can be established in people with earlystage KOA. Valuable variables for phenotyping are measures of nervous system sensitization and psychosocial features, while gait characteristics, quadriceps strength and comorbidities can add important information. Although no relation was found between pain phenotype models and pain worsening, phenotypes identified may lead to ease target treatment development for early-stage KOA patients.

Bibliography

Neelapala YVR, Neogi T, Kumar D, Jarraya M, Macedo L, Kobsar D, et al. Exploring diƯerent models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study. Osteoarthritis Cartilage. 2024 Feb;32(2):210–9.

Link to the full study

This article is a summary based on the following study. For further information and details, please consult the full study. Please do not hesitate to contact us if you have any comments. https://pubmed.ncbi.nlm.nih.gov/37709187/