Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints which possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.
In principal, changes of the synovial membrane can be inflammatory or non-inflammatory. To the latter group belong some benign tumors, such as tenosynovial giant cell tumor, lipoma or synovial chondromatosis. Rare non-inflammatory changes are the group of storage diseases. Inflammatory synovial diseases can be differentiated into crystal-induced arthropathy, such as gout and pseudogout, granulomatous diseases, such as tuberculosis, sarcoidosis and foreign body reactions and into the large group of non-granulomatous synovitis. This last group is by far the most common and often causes difficulties in assigning the histopathological findings to a definite diagnosis.
Hence, synovitis may occur in association with arthritis as well as lupus, gout, and other conditions. Synovitis is more pronounced in rheumatoid arthritis than in other forms of arthritis, and can thus serve as a distinguishing factor, although it is also present in many joints affected with osteoarthritis (OA).
Visco-supplementation is the process of injecting a gel-like substance into the joint. The substance is thought of as an additive to the joint fluid, thus lubricating the cartilage, and improving joint flexibility. This method of treatment, however, requires ongoing injections, as benefits are only temporary, because the currently used substances are degradable within weeks to months. Substances used in visco-supplementation include hyaluronic acid, or HA (Legend®, Hylartin® and
Synacid®, Synvisc, Euflexxa, Supartz etc) and poly-sulfated glycosaminoglycans (PSGAGS) such as Adequan®.
Polyacrylamide hydrogel (PAAG) is known for its ability to support cellular growth in vitro and allow in-growth of host tissue cells in vivo. This has been documented in the soft subcutaneous tissues of mice, rats, rabbits, pigs and humans. The tissue integration begins immediately after PAAG injection as a sort of foreign body reaction to the PAAG. Host macrophages and foreign-body giant cells initially surround the PAAG and then invade it. In the process these cells are gradually transformed into fibroblasts and endothelial cells, which eventually form a thin vessel-bearing fibrous network inside the PAAG. However, the integration of PAAG in these tissues was not associated with any luminal surfaces and the PAAG contained macrophages and giant cells up until 14 months post injection.
WO 02/16453 discloses the use of a polyacrylamide hydrogel (PAAG) for treating e.g. arthritis. where the treatment is considered to be based on a lubricating and cushioning effect of the hydrogel. WO 2012/123385 discloses use of PAAG in the treatment and/or prevention of joint swelling and/or bone oedema in a mammal suffering from arthritis. Neither WO 02/16453 nor WO 2012/123385 discloses prevention and/or treatment of synovitis in a mammal.
Christensen and Daugaard (J Arthritis 5: 217; Sep. 16, 2016) provide a case report on the histological appearance of the synovial membrane after treatment of knee osteoarthritis with polyacrylamide gel injections.
The common symptoms for all types of synotivis in mammals include varied levels of pain in mammals. Synovitis symptoms can be treated with anti-inflammatory drugs such as NSAIDs. Another possibility is injection of steroids directly into the affected joint. Specific treatment depends on the underlying cause of the synovitis. Common to the various types of existing treatment is that they all have their disadvantages, e.g. short term treatment, toxicity and side-effects.
Hence, there is a need for an alternative or improved way to prevent and/or treat synovitis in a mammal. Also, there is a need for an alternative or improved way to prevent and/or treat synovitis pain in a mammal.
Surprisingly, the present inventors have found that polyacrylamide hydrogel (PAAG) is useful in the prevention and/or treatment of synovitis. Without being bound by a particular theory, the analgesic effect on synovitis is considered caused by a stable, long-lasting sub-synovial layer of PAAG traversed with thin strands of connective tissue and changes to synovial cell composition or cytokine production. Accordingly, the present invention surprisingly demonstrated the formation of a novel synovial lining layer after integration of the PAAG into mammal joints that persisted for at least 24 months.