Abstract
BackgroundOsteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Inflammation of the infrapatellar fat pad (IFP) and synovial membrane (IFP surface) plays essential roles in persistent pain development in patients with OA. To identify the point during the inflammatory process critical for persistent pain development, we performed a time course histological analysis in a rat arthritis model.MethodsWistar rats received single intra-articular injection of monoiodoacetic acid (MIA, 0.2 or 1.0 mg/30 μL) in the right knees or phosphate-buffered saline (PBS, 30 μL) as a control in the left knees. Pain avoidance behaviors (weight-bearing asymmetry and tactile hypersensitivity of the plantar surface of the hind paw) were evaluated on days 0, 1, 3, 5, 7, and 14 after injection. Histological assessments of the knee joint were performed on days 0, 1, 3, 5, and 7 after MIA injection.ResultsWeight-bearing asymmetry was observed along with the onset of acute inflammation in both the low- (0.2 mg) and high-dose (1.0 mg) groups. In the low-dose group, weight-bearing asymmetry was completely reversed on day 10, indicating that joint pain seemed to alleviate between days 7 and 10. In contrast, we observed persistent joint pain after day 10 in the high-dose group. Histological assessments of the high-dose group indicated that the initial sign of inflammatory responses was observed in the perivascular region inside the IFP. Inflammatory cell infiltration from the perivascular region to the parenchymal region of the IFP was observed on day 3 and reached the IFP surface (synovial membrane) on day 7. Extensive fibrosis throughout the IFP was observed between days 5 and 7 after MIA injection.ConclusionOur data indicated that acute joint pain occurs along with the onset of acute inflammatory process. Irreversible structural changes in the IFP, such as extensive fibrosis, are observed prior to persistent pain development. Thus, we consider that this process may play important roles in persistent pain development.
Highlights
Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure
We noted the development of persistent pain in the high-dose model after 7 days [13]. We considered that these observations strongly suggested the importance of irreversible structural changes in the synovial membrane and infrapatellar fat pad (IFP) between 5 to 7 days during persistent pain development
These data suggest that some biological events that occurred between day 5 and 7 after monoiodoacetic acid (MIA) injection may play important roles during persistent pain development
Summary
Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Osteoarthritis (OA) is one of the most common diseases in aging societies, which is accompanied by chronic joint inflammation, articular cartilage degeneration, and osteophyte formation [1, 2]. The major complaint of patients with knee OA is persistent pain, which significantly decreases both, the patients’ activities of daily living (ADL) and quality of life (QOL). Some patients develop uncontrolled persistent knee pain with disease progression. In these cases, patients are pressed to make decisions for alternative treatments, such as total knee arthroplasty
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