# How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort

## TL;DR

This study explores how different types of knee osteoarthritis relate to patient-reported pain, finding that inflammation is more linked to pain severity than structural damage.

## Contribution

The study identifies distinct associations between inflammatory and structural subtypes of knee OA and specific pain outcomes using a large cohort.

## Key findings

- Systemic inflammation is significantly associated with higher pain scores in multiple pain questionnaires.
- Structural damage is linked to nociceptive-like pain as measured by PainDETECT.
- Meniscus/cartilage damage is significantly associated with lower PainDETECT scores.

## Abstract

To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI.

Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI.

The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ​≤ ​0.042 and β ​≥ ​0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ​≤ ​0.22 and β ​≤ ​−0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p ​= ​0.046 and β ​= ​−0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p ​= ​0.005 and β ​= ​−0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes.

For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies.