Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA)

Abstract

Objectives To address the hypothesis that different types of established OA pain behaviours have associations with different aspects of articular pathology, we investigated the relationship between structural knee joint pathology and pain behaviour following injection of a low versus a high dose of monosodium iodoacetate (MIA) in the rat. Methods Rats received a single intra-articular injection of 0.1mg or 1mg MIA or saline (control). Pain behaviour (hind limb weight bearing asymmetry (WB) and hindpaw withdrawal threshold (PWT) to punctate stimulation) was assessed. Cartilage and synovium were examined by macroscopic visualisation of articular surfaces and histopathology. Results Both doses of MIA lowered PWTs, 1mg MIA also resulted in WB asymmetry. Both doses were associated with cartilage macroscopic appearance, proteoglycan loss, abnormal chondrocyte morphology, increased numbers of vessels crossing the osteochondral junction, synovitis and macrophage infiltration into the synovium. PWTs were more strongly associated with chondrocyte morphology, synovitis and macrophage infiltration than with loss of cartilage surface integrity. Conclusions Both pain behaviours were associated with OA structural severity and synovitis. Differences in pain phenotype following low versus higher dose of MIA were identified despite similar structural pathology. OA structural pathology as traditionally measured only partially explains the MIA-induced pain phenotype