Preventing the pain of osteoarthritis – do molecules and proteins hold the answers?

Published by Arthritis Research UK | 22 August 2017

Fifty-seven percent of people with arthritis experience pain every single day. So, over the last year, we've renewed and strengthened a long-term commitment to cracking the big pain problem.

We pledged up to £5million of funding for new research focused on both prevention and treatment of pain and we brought together leading pain experts, key organisations and people with arthritis to help us devise an ambitious action plan for future pain research. By identifying and funding the research which gives the best chance of helping people with arthritis live fuller lives now, as well as preventing the pain of arthritis in the future, we hope to have the biggest impact on quality of life.

As a direct result of our Pain Challenge funding call, 13 new research projects will begin this year across the UK. In this edition, we’re focusing on two of those studies, both dedicated to understanding more about pain in the hope of developing breakthrough treatments for osteoarthritis.

Can a single molecule prevent pain and repair cartilage?

Researchers at Queen Mary University of London are embarking on a five-year study to discover more about the role of the molecule agrin in the cause and treatment of osteoarthritis.

Agrin is found in nerves and muscles, however researchers at the university found cartilage also contains agrin. They discovered this important molecule is essential to cartilage health, bringing about cartilage healing, but is lost from the cartilage of patients with osteoarthritis. So, this study will explore if restoring or supplementing the agrin in our bodies will simultaneously treat the pain of osteoarthritis and regenerate cartilage

Professor of Musculoskeletal Regenerative Medicine and Rheumatology Francesco Dell’Accio and Dr Suzanne Eldridge, who are conducting the study, said: "People with arthritis experience two main types of pain. Firstly, there’s the pain that tells us we’re hurting ourselves and need to stop to avoid more damage; for example, the pain we get if we bang a knee into a table, burn ourselves or overload our joints carrying a heavy box. This pain is useful and necessary.

"However, agrin is linked to a different and more problematic type of pain – the pain we feel when things that aren’t normally painful become painful. This is called 'pathological' pain and is caused by oversensitive nerves or changes in the way our brains process messages from the rest of the body.

"We know the loss of agrin makes things that shouldn’t hurt us more painful, but we need to find out how and why? If we can build our understanding and find a safe and effective way to replace agrin, we move one step closer to being able to develop a treatment that targets and takes away this type of pain only. This is important because, though we have excellent painkillers there's a risk these drugs block the good, as well as the pathological, pain. Creating a targeted treatment for this 'bad' pain would be a significant breakthrough in the treatment of osteoarthritis."

The generation that will develop better treatments for osteoarthritis

"Creating a targeted treatment for this 'bad' pain would be a significant breakthrough in the treatment of osteoarthritis."The research team will work in the lab with mice to look at the effects of adding and taking away agrin on cartilage repair and pain responses. They'll also use cartilage donated by patients who have had a joint replacement to find out more about the impact of agrin breakdown on pain and osteoarthritis.

Professor Dell’Accio and Dr Eldridge continue: "It's fascinating that a single molecule can potentially help to repair damaged cartilage and remove pain. As clinicians as well as researchers, we find it extremely distressing to see patients with osteoarthritis and not be able to offer them a solution. We know the impact pain has on the quality of people’s everyday lives and this inspires us to go back to the lab and find answers."

"We feel this is the generation that will develop better treatments for osteoarthritis. We're getting there and believe there's light at the end of the tunnel because finally we understand more about how cartilage damage occurs and how the body can repair itself. This improved understanding, developed over the last decade, means we have identified targets for drugs that can stop the progression of osteoarthritis and even regenerate damaged cartilage in animals with osteoarthritis.

"Unfortunately, not all these drugs have been suitable to try in patients. But now we know it's possible and it's only a matter of time before we can adapt and refine our research findings to help people with osteoarthritis.

"There was a time when if you had cartilage damage it simply couldn’t be fixed and I’m confident this is going to change. We know the cells are there, our research is about learning their language to understand more about the way they work."

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This study also includes several collaborators, including members of the Arthritis Research UK Centre of Excellence for Pain (Professor Victoria Chapman and Dr. Federico Dajas-Bailador) and of the Arthritis Research UK Centre of Excellence for Osteoarthritis Pathogenesis (Professor Tonia Vincent).

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Nerve protein may protect against the onset and pain of arthritis

Meanwhile, another three-year study will explore if a protein found on nerves in and around our joints could be used to reduce pain and inflammation associated with osteoarthritis.

Susan Brain, Professor of Pharmacology at King’s College London, tells us more about why her team is conducting this research: "We've identified a protein found in our bodies which we hope could protect against the onset and pain of arthritis. Our research so far suggests when there’s a high level of this protein, called TRPC5, around our joints we feel less pain and when there’s not enough of it we're likely to see increased pain and arthritis.

"To explore this in more detail we've developed a chemical substance which can replicate the way the body naturally stimulates this protein. This will allow us to artificially increase levels of TRPC5 activity in and around the joints and look at the impact this has on pain and arthritis. In the long-term, and depending on what we discover, there's potential to use this as a drug to treat painful symptoms and stop the progression of arthritis.""In the long-term, and depending on what we discover, there's potential to use this as a drug to treat painful symptoms and stop the progression of arthritis."Professor Susan Brain

The researchers will work with mice with different levels of TRPC5 and arthritis to observe their responses. Human DNA samples donated for medical research will also be used to learn more about TRPC5. Each DNA sample is accompanied by in-depth information about their medical history and experience of pain allowing the research team to identify the DNA of people with osteoarthritis, separating out those with the condition who have chronic pain and those that don’t.

Professor Brain says: "Studying these DNA samples and looking at what’s happened to the TRPC5 within them will help us to discover if there are any alterations to the genetic sequence that help to explain why some patients have pain and others don’t."

"More and more people are going to have osteoarthritis as we live for longer. Working on research which has the potential to change the lives of people with the constant, chronic pain of osteoarthritis is a big driving force for me. If you look at the drugs available to treat pain there are very few new ones.

"We need more funding and collaboration to energise and inspire pain research which leads to the development of better treatments. That’s why Arthritis Research UK is doing such an important job."

Read our guide to living with and managing long-term pain.

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