E045 Role of Thrombospondin-4 in pain sensitisation of knee osteoarthritis in relation to semi-automated joint space measures in routine radiographs

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Abstract Background/Aims Pain and stiffness in knee osteoarthritis (OA) is linked to inflammation and structural damage. The source of OA pain is not fully established and a better understanding is required for individually optimised treatments. Many patients cycle through treatments including analgesics and steroid injections but those with pain sensitisation may be less responsive to conventional therapies. Thrombospondin-4 (TSP-4) is a glycoprotein found in the extra-cellular matrix and neuromuscular junction. Its increased expression promotes neuropathic pain and central sensitisation in rodents, and is found elevated in cartilage and bone marrow lesions (BMLs) in humans with knee OA. We hypothesise elevated TSP-4 results in pain sensitisation and we investigate how variation in pain relates to serum TSP-4, clinical variables and joint space (JS) measures. Methods TSP-4 was measured in serum samples from participants with knee OA patients using ELISA (ELH-TSP-4, RayBiotech, Tebubio, UK ) with full informed consent, along with age, sex, body mass index (BMI), Hospital Anxiety and Depression Scale (HADS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales of pain and stiffness, and PainDETECT scores. Kellgren-Lawrence grade (KLG) and JS were measured semi-automatically from medial and lateral regions using plain OA knee radiographs. A general linear model (GLM) with age, BMI and HADS as base covariates, was used to investigate which of sex, TSP-4 and JS parameters contributed significantly to variability in WOMAC and painDETECT scores. Results Of 93 patients studied, 25 were male, 68 female, with mean [range] scores: WOMAC pain 54.9 [2, 98]; WOMAC Stiffness 59.3 [0, 99.5]; painDETECT 12.7 [0, 28)]. Table 1 shows parameter ranges for other variables used in the GLM and those significantly contributing to variability in WOMAC and painDETECT scores. Conclusion TSP-4 was a highly significant (p < 0.001) contributor to variability in pain and sensitisation, and to stiffness. Sex and JS were additional factors affecting stiffness. TSP-4 is a potential biomarker for objectively quantifying pain along with structural measures from imaging. Our work suggests that people with OA and pain sensitisation can be stratified using serum TSP-4, which could aid in better disease management and clinical decision-making for future OA treatments. Disclosure A. Law: None. S. Koushesh: None. A. Harrison: None. K. Seyi-Taylor: None. A. Niakan: None. R. Ljuhar: Corporate appointments; CEO ImageBiopsy Lab. Shareholder/stock ownership; Shareholder of ImageBiopsy Lab. N. Sofat: None. F.A. Howe: None.

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