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

Abstract

SummaryObjectivesTo address the hypothesis that different types of established osteoarthritis (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 vs a high dose of monosodium iodoacetate (MIA) in the rat.MethodsRats received a single intra-articular injection of 0.1 mg or 1 mg 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.ResultsBoth doses of MIA lowered PWTs, 1 mg 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.ConclusionsBoth pain behaviours were associated with OA structural severity and synovitis. Differences in pain phenotype following low vs higher dose of MIA were identified despite similar structural pathology. OA structural pathology as traditionally measured only partially explains the MIA-induced pain phenotype.

Impaired chronic pain‐like behaviour and altered opioidergic system in the TASTPM mouse model of Alzheimer's disease

“…Despite these behavioural observations, knee joint pathology in the form of degradation of articular cartilage accompanied by inflammation in the synovial membrane was exhibited by both the TASTPM and WT mice 4 weeks post‐MIA administration. Intra‐articular administration of MIA has been shown to display mechanical hypersensitivity in the absence of weight bearing deficits in a dose‐dependent manner, despite the knee joint pathologies (Ogbonna et al., ; Nwosu et al., ). Therefore, mechanical hypersensitivity and absence of ongoing pain exhibited by the transgenic model of AD may suggest a possible alteration of central plasticity mechanisms of MIA‐induced OA pain.…”

Cartilage Tissue Engineering and Regeneration

“…The development of experimental models for OA is of fundamental importance for the understanding of the pathophysiology of the pathology, for example, through experimental models in rats as shown in Figure 3; it was possible to observe a much more complex relation between the histological morphology of the cartilaginous tissue and the pain phenotypes. It can contribute significantly in understanding the mechanisms of cellular development and interaction in diseased joints as well as in the targeting of patients' analgesic therapy [21].…”

Recent developments in emerging therapeutic targets of osteoarthritis

“…Similar assessments have been frequently made in chemical models of osteoarthritis such as those induced by intra-articular monoiodoacetate (MIA) injection; however, the disease progression in these models develops far more rapidly than surgical models [68 ▪▪ ]. A recent study examining pain-related behaviors in rats with bilateral intra-articular injection of MIA demonstrated that decreased spontaneous animal burrowing is correlated with spontaneous animal activity and rearing indicative of pain [69 ▪▪ ].…”