Inflammation drives painful sensitization in knee osteoarthritis

Osteoarthritis, or OA, is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage -- the cushioning material at the end of long bones -- and causes changes in the structures around the joint. These changes can include fluid accumulation, bony overgrowth, and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.

Knee osteoarthritis is a common form of osteoarthritis and is caused by cartilage breakdown in the knee joint. Factors that increase the risk of knee osteoarthritis -- including being overweight, age, injury or stress to the joints, and family history -- can increase the risk of knee osteoarthritis.

Sensitization refers to an alteration of the nervous system that results in heightened pain sensitivity, and may play an important role in knee OA pain. Because inflammation and/or tissue injury are thought to contribute to sensitization, U.S. researchers set out to learn whether this was the case in human knee OA. They specifically studied whether inflammation-related lesions in knee OA, such as synovitis or effusion, or mechanical load or remodeling due to non-inflammatory bone marrow lesions (a marker of tissue injury), are risk factors for increased sensitization in knee OA.

"It is widely recognized that the level of pain patients experience is not always what one would expect based upon what is seen on their X-rays," said Tuhina Neogi, MD, PhD, FRCPC of Boston University School of Medicine and a lead author on the study. "In prior work, we have found that sensitization is associated with greater pain severity and may explain part of this discrepancy between pain levels and X-ray changes. However, we still did not understand why some people exhibit sensitization while others do not. If we could understand why sensitization occurs in some people with knee OA, then that could be a potential target for treatment that could ultimately reduce the severity of pain experienced by those individuals."

Using data from the Multicenter Osteoarthritis (MOST) Study, researchers in the U.S. looked at test results obtained from 1,111 subjects with or at risk of knee OA, including X-rays, magnetic resonance imaging scans (MRI), and standardized somatosensory evaluations of two measures that give insights into the presence of sensitization: mechanical temporal summation and pressure pain thresholds (PPT). These measures were obtained at the knee at baseline and again two years later. The mean age of the subjects in the study was 66.9. The mean BMI was 29.7, and 62 percent were female.

The researchers looked at how synovitis, effusion and BMLs seen at the baseline assessment might be related to the new development of temporal summation in the same knee 2 years later among those who did not show signs of it at the baseline visit. They also assessed changes in PPT levels in the same knee between baseline and the visit two years later in all the subjects.

Of the 1,111 subjects studied, 22.6 percent developed incident temporal summation by the 2-year study visit. Between the baseline and two-year visit, changes in the PPT levels ranged from -7.35 to 7.15 kg/cm2. Synovitis was associated with significant decreases in PPT (i.e., more pain sensitive). Effusion was significantly associated with incident temporal summation. Bone marrow lesions presence or burden was not associated with temporal summation or change in PPT.

The study's authors concluded that inflammation, such as that associated with synovitis or effusion, may drive sensitization in knee OA, while BMLs do not appear to do so. They suggested that early targeting of inflammation in knee OA may prevent sensitization and helping to reduce pain severity in people with knee OA.

"This is the first such study in knee OA to obtain sensitization measures at more than one time-point in such a large number of individuals, providing insights for the first time into how sensitization may develop or change over time in this disease," said Dr. Neogi. "These results will help broaden understanding of how and why pain may evolve in people with knee OA and help identify potential treatment targets for pain in knee OA -- a disease that affects millions of people, yet has very few effective treatment options."