Pathophysiology of arthritis pain
Osteoarthritis is a disease most often seen in older individuals but it also may occur in younger people, following injury or repetitive stress. More than 80% of people older than 75 have clinical OA, and more than 80% over the age of 50 have x-ray evidence of OA The joint consists of bone, cartilage, and connective tissue. Subchondral bone is covered by hyaline or articular cartilage that consists of type II collagen, chondrocytes and proteoglycans which are high molecular weight glycoproteins that retain water and thereby increase resiliency of cartilage. Collagen fibrils are arranged in an arcade which provides tensile strength, and the proteoglycans provide distensibility by retaining adequate hydration. The synovial cell layer that lines the joint produces a viscous synovial fluid that lubricates joint motion.
Superficial to the synovial membrane is a flexible joint capsule with ligaments and tendons. Outside the joint, bursae provide a smooth surface for muscle, tendon, and ligaments to pass over roughened bone surfaces. These joint components provide for both motion and load bearing across nearly frictionless surfaces, and any or all of these joint components are involved in the osteoarthritis process depending on the extent of the disease.
OA is primarily a disease of cartilage that produces a local tissue response, mechanical change, and failure of function. The disease typically affects weight-bearing joints asymmetrically. More recently, an association has been established between OA and typically local low-grade inflammation with few systemic effects. The osteoarthritis process can result from excessive or repetitive loading of the normal joint, including work-related repetitive activities that damage cartilage or subchondral bone, trauma, or increased load to the joint from chronic obesity. This process may occur in the context of either inherently abnormal cartilage or of a specific insult to the structure of cartilage leading to increased susceptibility.
As cartilage is damaged, it becomes thinner, develops fissures or large clefts, and proteoglycan synthesis decreases. That process leads to further decreased cartilaginous load-bearing capacity. The chondrocyte in cartilage can respond initially by attempting to repair its surrounding extracellular matrix, but as it is overwhelmed there is increased release of neutral metalloproteinases and lysosomal proteases leading to further matrix loss and ultimately increasing the destructive cascade.
By contrast, lets now look at another type of arthritis.
Rheumatoid arthritis (RA) has a different pathophysiology. RA begins in the synovium and systemic extra-articular manifestations may include fever, weight loss, skin thinning, scleritis, corneal ulcers, and the formation of subcutaneous or subperiosteal nodules. Multiple organs may be involved leading to premature death. The etiology of RA is unknown. Possibilities include various viral or bacterial infections or infection with mycobacteria. An environmental event, perhaps viral particles or bacterial proteins, stimulates An immune response in the appropriate genetic host leading to a host immune response that may cross react with similar antigens in the host joint tissue. There are other possible explanations of the environment interacting with the appropriate host.
When dendritic cells, monocytes, and macrophages are activated by the autoimmune process, they interact with and present antigen to the appropriate T cells. A series of events occurs that leads to the further activation of more monocytes and macrophages, T cells, B cells, and increased endothelial cell activity. These events increase the synthesis of adhesion molecules, leading to the increased vascular margination of mononuclear cells. Polymorphonuclear cells are attracted to the inflamed joint fluid by the elaboration of multiple cytokines, some of which act as chemoattractants that increase the delivery of inflammatory cells to the synovium and synovial fluid. Cytokines such as IL-1 alpha or beta, IL-8, tumor necrosis factor (TNF)-alpha, platelet-derived growth factor, heparin binding growth factor, GM-CSF, IFN-gamma, TGF-beta, IL-2, and IL-6 lead to increased activation of fibroblast-like cells in the synovium and chondrocytes, as well as other macrophages. The activation releases increased amounts of prostaglandins, neutral proteinases such as collagenases, transin/stromelysin, and recruits osteoclast precursors, which culminate in the destruction of bone and cartilage by the invading proliferative synovium.
Therefore, RA is a progressive destructive inflammatory disease of the synovium. Release of cytokines and other pro-inflammatory mediators and proteinases lead to the destruction of the joint.
Other forms of arthritis have other types of pathophysiology. For example, gout is an inflammatory arthritis that is induced by crystals of monosodium urate.
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