Background Pain is the major symptom of knee osteoarthritis (OA) and is usually the reason sufferers first seek clinical assistance; however the precise relationship between tibiofemoral pathology and OA pain is not entirely clear. Although magnetic resonance imaging (MRI) studies have linked pain to synovitis, subchondral changes and meniscal abnormalities, the histopathological features specific to symptoms in OA are not well understood.
Objectives To identify which histological features are associated with symptomatic human knee OA. Better understanding of pain-associated structural and biochemical modifications is crucial for the development of more targeted and effective analgesic treatments.
Methods Medial tibial plateaux and synovia were obtained from post-mortem (PM) cases who had not sought help for knee pain and from patients undergoing total knee replacement (TKR) surgery for symptomatic OA. The Academic Rheumatology joint tissue repository (n >2000) was screened to select TKR and PM cases displaying similar macroscopic joint chondropathy (n = 29/group). Tissues were compared to identify which histological features were associated with painful OA, assuming TKR cases experienced greater levels of knee pain than PM. OA changes (Mankin score) and synovitis were histologically graded and CD68-positive macrophages and nerve growth factor (NGF) quantified using immunohistochemistry and computer-assisted image analysis.
Results Synovitis, loss of cartilage surface integrity, proteoglycan loss, tidemark breaching and subchondral changes were all characteristic features of end-stage OA. In the current study, TKR and PM cases were matched for similar macroscopic chondropathy scores (207 v. 196, respectively, P > 0.05). Total knee replacement cases (median age 68 years, 55% male) were slightly younger (P < 0.05) than post-mortem cases (median age 71 years, 55% male). Synovial fractional area positive for NGF was increased in TKR compared with PM cases (13.9% vs. 9.3%, P = 0.021). Synovitis score and loss of cartilage surface integrity were also greater in the surgical group (P = 0.001 and 0.014, respectively), although CD68 fractional areas did not differ significantly between groups (P = 0.21). Adjusting for age differences did not affect the results.
Conclusions Symptomatic OA is associated with increased synovial NGF expression, synovitis and loss of cartilage surface integrity compared to PM cases with similar macroscopic joint surface appearances who did not seek TKR. Synovial NGF may be a key inflammatory mediator associated with OA knee pain. Identifying structural, cellular and molecular signatures of symptomatic OA may lead to targeted treatment strategies in the future.
Disclosure of Interest None Declared
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