The FRAME Alternatives Laboratory has recently worked with the Arthritis Research UK Pain Centre, which is also based at the University of Nottingham, to study biomarkers associated with symptomatic and asymptomatic osteoarthritis of the knee.
The study used synovial membrane samples from the knees of post-mortem cases and knee replacement patients. Tissue samples were used where knee replacement had occurred after little or no knee damage and where there was a lot of knee damage, but there had been no knee replacement, indicating low levels of pain.
The synovium was then studied for evidence of gene and protein changes that can be associated with pain and inflammation. The data from this study aims to help develop a better understanding of which inflammation-associated molecules mediate osteoarthritis pain and should help refinement of existing therapies and development of new treatments.
Some research into osteoarthritis, which is the most common form of arthritis, uses case studies but much of it still uses animals.
One common model used to reproduce the physical characteristics of osteoarthritis and associated pain symptoms in rats involves a surgical incision into the rat’s knee. This causes damage through mechanical injury. Another model involves the chemical, MIA (mono-iodocetate) being injected into the knee joint to destroy cartilage producing cells.
Although these models both successfully recreate osteoarthritic pain in rats, the expected correlation between osteoarthritic knee damage (measured by a chondropathy score) and pain does not exist in humans. There are cases where people have knees with little or no obvious damage (low chondropathy score) yet suffer from severe pain, and others where people have obvious severe knee damage (high chondropathy score) but suffer from little or no pain.
Dr Andy Bennett, Director of the FRAME Alternatives Laboratory, said: “The driving factor behind knee transplant surgery is not the damage or stability of the knee, but the pain suffered. Therefore, animal models are of limited use if we want to gain understanding of the causes of knee pain in osteoarthritis patients.
“This research is an example of how some animal models struggle to accurately replicate conditions found in the human body. Although research using animals may provide some insight, animal models fail to reflect the individual nature of human patients. The ability to study disease in human subjects will ultimately shed more light on the condition, its prevention and treatment.”
The unique location of the FRAME Alternatives Laboratory within the University of Nottingham Medical School allows our scientists to work closely with clinicians from the Nottingham University NHS Trust. This gives the laboratory access to primary human cells to produce in-vitro models and also the opportunity to collaborate on human-based studies.