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Osteoarthritis (OA) is the most common form of arthritis and affects more than 20 million Americans.

There are two different types of cartilage within the knee. Hard hyaline articular cartilage is the tough gristle that caps the ends of long bones within the joint. Also located on either side are two semicircular pieces of fibrocartilage, a somewhat softer form of cartilage, called menisci.

OA is primarily a disease of the hyaline cartilage. Hyaline cartilage is made up of a matrix consisting of a combination of proteoglycans (complexes of proteins and sugars) and chondrocytes. Chondrocytes are located within the matrix... picture a gelatin mold with grapes. The gelatin is the matrix and the grapes are the chondrocytes. Chondrocytes are cartilage cells that manufacture matrix under normal healthy circumstances. They are responsible for nourishing the matrix as well.

However, when OA develops, a change in the metabolism of hyaline cartilage occurs. Chondrocytes begin to elaborate destructive enzymes causing cracks and fissures in the cartilage. These are called "fibrillations."

What has been a perplexing question is, "What causes pain in OA of the knee?" Cartilage has no blood vessels nor does it have nerves. So the topic of pain mechanism in osteoarthritis has been the subject of intense interest.

There are a number of potential suspects. For example, when osteophytes (bone spurs) develop, they can lift the periosteum (the thin top layer of the bone). Periosteum is rich in nerve fibers and certainly can be a source of pain.

It has been noted that blood vessels in bone underlying osteoarthritic cartilage can become engorged and this may elevate the pressure inside the bone which could also, theoretically, cause pain.

The lining of the joint (synovium) becomes inflamed in OA. Pain fibers are located within the joint capsule and these inflammatory processes could irritate them.

The joint capsule can contract or shrink leading to irritation of nerve fibers located within the capsule.

By the same token, if fluid builds up within the joint, it can stretch the joint capsule again leading to stimulation of pain fibers.

As mentioned earlier, there are two small pieces of fibrocartilage located within the knee. These pieces of fibrocartilage (menisci) have a rich blood and nerve supply where they attach to the joint capsule. OA often leads to tearing of these menisci. This can cause damage to the capsular attachment leading to pain.

Spasm of the muscles surrounding the knee can also lead to pain.

Finally, there is increasing interest in the role of the central nervous system- the brain- in causing the pain of knee OA. Recent studies showing the effectiveness of drugs like Cymbalta, a drug originally prescribed for depression, but also showing beneficial effects on pain relief in patients with OA, led to FDA approval for this indication in 2011.

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