Lubricating Fluid in the Knee May Play a Role in Osteoarthritic Pain

Researchers from the University of Cambridge have recently found that the knee’s lubricating fluid may trigger a pain response in patients with osteoarthritis (OA). This work was carried out by a team at the University of Cambridge and found that the OA patient’s synovial fluid, which normally provides the knee with lubrication, may express unique qualities that fuel painful inflammation. This work was published in the journal Rheumatology on August 13.

OA is the most common form of arthritis, characterized by degenerative changes in the joint’s cartilage. Normally the cartilage functions to minimize friction in the joint capsule but over time as this cartilage wears away the bone beneath becomes exposed. When this occurs in the knee, the femur and tibia encounter little or no cartilage between them, producing the painful inflammation of arthritis. OA accounts for millions in costs, both directly through healthcare and indirectly due to the disease’s impact on the patient’s occupational ability.

“Osteoarthritis can be a very painful condition, but we only know a little about what causes this pain,” said Sam Chakrabarti, a Gates Cambridge Scholar. “We wanted to investigate what was happening in the joint and to see whether it was the lubricant that ordinarily keeps these joints moving that was contributing to the pain. Studies such as these are important in helping us develop better treatments.”

This debilitating condition typically manifests in the patient’s later years, often due to “wear and tear” of the cartilage over time. Research from pharma leaders Pfizer and Eli Lily has found that the anti-inflammatory drug tanezumab yielded pain for OA patients in a phase 3 clinical trial, highlighting inflammation’s role in OA symptoms.

When this inflammation occurs, an increased number of cells are produced within the joint. These cells release inflammatory agents into the synovial fluid, causing the volume of the joint capsule to increase. The synovial fluid becomes less viscous and these inflammatory molecules meet sensory nerves during osteoarthritis, producing the perceived pain.

Background of the Cambridge Study

In their study, researchers from at the University of Cambridge and Addenbrooke’s Hospital, part of Cambridge University Hospitals, evaluated whether the synovial fluid of OA patients contributes to this sensory nerve stimulation.

First, the team extracted synovial fluid from Addenbrooke patients with OA and from post-mortem donors with no diagnosed joint disease. They then exposed healthy sensory nerves from the knees of mice to either the OA synovial fluid or the healthy fluid samples.

Upon incubating the nerves in the OA synovial fluid, the researchers found that they were easier to stimulate. These nerves also showed an increase in TRPV1 function, a molecule that elicits a painful, burning sensation. Though researchers have known for over 60 years that inflammatory molecules are present in the synovial fluid of OA patients, this study is the first to show that the fluid itself can directly excite sensory neurons. Through this mechanism, the OA synovial fluid plays an important role in creating pain.

“This is the first time we have been able to use synovial fluid from human osteoarthritis patients to excite sensory nerve cells, making it more clinically-relevant than mouse studies alone, and so will hopefully help translating treatments from bench to bedside,” explained Dr. Ewan St John Smith, Department of Pharmacology at the University of Cambridge.

These researchers note that this model can be used to identify specific aspects of synovial fluid that causes pain, allowing scientists to test how a drug could combat arthritic pain in the future.

“Since synovial fluid is regularly collected from arthritic patients as part of their treatment regime, our technique can be easily set up in laboratories throughout the world to understand and help to identify a cure for arthritic pain,” said Smith.

Dr Deepak Jadon, Director of the Rheumatology Research Unit at Cambridge University Hospitals, noted that this work was the result of cooperation between patients, researchers, and physicians.

“This study highlights how much we can learn with the help of our patients, as well as the importance of collaboration between clinicians and basic scientists,” said Jadon.