A team at the 探花直播 of Cambridge has shown how, in osteoarthritis patients, the viscous lubricant that ordinarily allows our joints to move smoothly triggers a pain response from nerve cells similar to that caused by chilli peppers.

In the future, this set up can be used to identify the specific components of synovial fluid that cause pain

Ewan St John Smith

Osteoarthritis is the most common form of arthritis. It causes joint pain and stiffness, and in some people swelling and tenderness of the joints. 探花直播condition affects an individual鈥檚 quality of life and costs millions to the global economy, both directly in terms of healthcare costs and indirectly due to impact on the individual鈥檚 working life.

Osteoarthritis tends to occur later in life and has been largely considered as a degenerative disorder in which pain is produced by damage and wear and tear to bone and cartilage. However, in recent years it has become clear that osteoarthritis is not restricted to cartilage damage, but is a failure of the entire joint, with inflammation 鈥 the body鈥檚 response to stress and injury 鈥 being a major contributor to the pain experienced by patients. A recent collaboration between the two pharmaceutical companies Pfizer and Eli Lilly has found that their anti-inflammatory drug, tanezumab, produced pain relief for osteoarthritic patients in a phase 3 clinical trial.

When inflammation occurs during osteoarthritis, the body produces an increased number of cells within and around the joint. These cells release inflammatory substances into the synovial fluid, the lubricant that allows joints to move smoothly. During osteoarthritis, synovial fluid becomes less viscous and these inflammatory substances come into direct contact with sensory nerve cells in the joint, producing the sensation of pain.

In a study published on 13 August 2019听 in the journal Rheumatology, researchers at the 探花直播 of Cambridge and Addenbrooke鈥檚 Hospital, part of Cambridge 探花直播 Hospitals, examined whether synovial fluid produced during osteoarthritis is capable of directly exciting sensory nerves supplying knee joints 鈥 those nerves responsible for transmitting pain signals.

鈥淥steoarthritis can be a very painful condition, but we only know a little about what causes this pain,鈥 says Sam Chakrabarti, a Gates Cambridge Scholar. 鈥淲e 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.鈥

探花直播researchers obtained synovial fluid from consenting osteoarthritis patients at Addenbrooke鈥檚 Hospital and from post-mortem donors with no known joint disease. They then incubated knee sensory nerves isolated from mice in either healthy or osteoarthritis synovial fluid and recorded the activity of these nerves.

探花直播team found that when incubated with osteoarthritic synovial fluid, the knee nerves were more excitable. 探花直播nerves also showed an increase in the function of TRPV1, a molecule that detects the hotness of chilli peppers (TRPV1 is also activated by heat, which is why chillis tastes hot). Although the presence of inflammatory chemicals in osteoarthritis synovial fluid has been known since 1959, this is the first evidence that synovial fluid can directly excite sensory nerves and hence is an important contributor to an individual鈥檚 experience of pain.听

鈥淭his 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,鈥 says Dr Ewan St John Smith from the Department of Pharmacology at the 探花直播 of Cambridge.

鈥淚n the future, this set up can be used to identify the specific components of synovial fluid that cause pain and then to test if and how a drug will be useful in arthritic pain. 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.鈥

Dr Deepak Jadon, Director of the Rheumatology Research Unit at Cambridge 探花直播 Hospitals, adds: 鈥淭his 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.鈥

探花直播research was funded by Versus Arthritis and the Gates Cambridge Trust.

Reference

Chakrabarti, S et al. . Rheumatology; 13 August 2019; DOI: 10.1093/rheumatology/kez331

Researcher profile: Sampurna Chakrabarti

Around the time that Sam Chakrabarti graduated from the 探花直播 of Buffalo, the State 探花直播 of New York, the US was caught in the middle of the opioid crisis, in part because these addictive pain killers were being over-prescribed. Spurred on by the crisis, Sam joined the lab of Dr Ewan St John Smith at Cambridge as a Gates Cambridge Scholar, eager to improve the lives of other by furthering the understanding of pain pathways. 鈥淚 want my research to contribute towards a world where pain relief is safe and affordable, a world where the reason people take time off work is to go on vacation, not because they are in excruciating pain,鈥 she says.
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Originally from Kolkata, India, Sam is interested in finding better ways of studying painful knee arthritis to help identify drug targets. Arthritis affects millions of people worldwide, but patients often receive inadequate pain relief.听A听major reason for this is the lack of understanding of the basic biology underlying the disease,听but Sam recognizes that tackling arthritic pain will require a much broader approach than basic science.听
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鈥淚 hope my research will lead to an understanding of pain that crosses many disciplines and breaks down the language barrier between psychologists, biologists and computer scientists,鈥 she says. 鈥淧ain is complex and manifests at multiple levels 鈥 a way to understand a phenomenon like this should also be multidisciplinary.鈥
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Sam has been at Cambridge since 2016, during which time听she says:听鈥淚 have met more fascinating, inspiring and engaging people than in my entire life.听At Cambridge I feel I am a part of the quest for knowledge that transcends grades and papers, but reflects our innate curiosity.鈥


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