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The £3.9M Wellcome Collaborative Award will be used to identify the drivers of pain in people living with rheumatoid arthritis.

Doctor examining hand of patient with rheumatoid arthritis © SHUTTERSTOCK

Professor Leonie Taams and Dr Franziska Denk from King's College London, and Professors Christopher Buckley from the Kennedy Institute at NDORMS, and David Bennett from the Nuffield Department of Clinical Neurosciences, Oxford, have secured a multimillion-pound Wellcome Collaborative Award for their study 'Fibroblasts as key drivers of persistent pain in inflammatory arthritis'.

Many people with rheumatoid arthritis (RA) live with pain every day, even when their inflammation is well-controlled through medication. Much research on how RA pain persists is focused on the brain sending faulty signals that are experienced as painful. However, another hypothesis is that pain is continually caused in patients' joints by local cells called fibroblasts. Immunologists have shown that fibroblasts are hyperactive in arthritis and make factors that can interact with nerves, yet scientists lack detailed knowledge of the process and how it affects pain. The interdisciplinary team aims to address this gap.

Professor Leonie Taams said: "I am absolutely delighted with the award of this collaborative grant. For many years, my lab has been researching the cellular and molecular mechanisms that drive inflammation in rheumatoid arthritis; through this collaboration with eminent pain biology and fibroblast experts we can now turn our attention in earnest to the factors that drive pain in rheumatoid arthritis. This research will address a major unmet need for people living with the disease who frequently tell us about the impact of pain on their lives."

The researchers intend to show that human fibroblasts can affect nerves negatively, identify which type of fibroblast is most important in this process and identify which fibroblast factors might make good painkillers.

Christopher Buckley said: "Despite the spectacular success of new biologic therapies (such as anti-TNF) that suppress inflammation, such treatments do not adequately control pain which continues to remain an important issue for people with arthritis. In the past it was thought that inflammation and pain were coupled such that if inflammation was abolished then pain would be suppressed. Recent work has suggested that pain and inflammation are not always coupled and that drugs that target the cells that make up the structure of joints (fibroblasts) rather than immune cells may be more effective at treating joint pain."

The four collaborators were inspired by their mutual research interests as well as by conversations with patients who live with rheumatoid arthritis.

"I'm very grateful to the Wellcome Trust for recognising the importance of interdisciplinary research and for supporting our proposal," said Dr Franziska Denk. "I look forward to working with our wonderful team, including our clinical partners and patient experts who have inspired us to develop this bid."

Professor David Bennett continued: "Although treatments for rheumatoid arthritis have undoubtedly improved over the last two decades chronic pain remains a huge problem for those living with the disease. I look forward to working with my cross-disciplinary colleagues in Oxford and King's College London in order to better understand and ultimately improve the management of such pain."

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