Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint

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.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2391-1) contains supplementary material, which is available to authorized users.

Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model

“…The rodent MIA-induced arthritis model has been used to assess pathological progression of the disease, pain behavior, and peripheral nerve sensitization. 16,17,32,37 Injection of high-dose MIA (1.0 mg per joint) into the knee induces irreversible structural changes in the IFP and persistent pain, whereas low-dose MIA (0.2 mg per joint) does not induce structural changes or persistent pain. 16,37 Therefore, we considered that the levels of pain in the high-dose MIA-induced arthritis model are highly reproducible and that the model is suitable for assessing the effect of anti-inflammatory therapies on pain and histological changes of synovium and IFP.…”

Platelet‐derived growth factor receptor‐β (PDGFRβ) lineage tracing highlights perivascular cell to myofibroblast transdifferentiation during post‐traumatic osteoarthritis

“…Frozen sagittal sections at the level of the posterior cruciate ligament were stained with Masson's trichrome stain. Semiquantitative evaluation was performed according to the method previously described 19 . In short, score 0 indicates normal (fibrosis is less than 20% of total area), score 1: low (20%‐40%), score 2: high (40%‐60%), score 3: extensive (more than 60%).…”

“…Semiquantitative evaluation was performed according to the method previously described. 19 In short, score 0 indicates normal (fibrosis is less than 20% of total area), score 1: low (20%-40%), score 2: high (40%-60%), score 3: extensive (more than 60%). All scoring were performed blinded to the treatment group.…”

“…19 The lower region of the IFP was defined as the perivascular area. 19 All quantifications were based on random 10× field images. All morphometric analyses were performed blinded to the treatment group.…”

“…For this purpose, the IFP was separated for analysis into adipose and perivascular areas (19) (Figure 3B (Figure S1A). Thus, transient and robust α-SMA expression is observed within the IFP, including within mGFP+ pericyte descendants.…”