Understanding why pain persists when inflammation has resolved

Disease - Rheumatoid arthritis

Lead applicant - Professor Marzia Malcangio

Organisation - King's College London

Type of grant - Invited Research Award

Status of grant - Active

Amount of the original award - £262,327.28

Start date - 3 September 2018

Reference - 21961

Public Summary

What are the aims of this research?

Pain is a persistent symptom of rheumatoid arthritis it is often one of the first symptoms that people experience, and it remains even after swelling has been reduced with treatments. This implies that other mechanisms, outside of the joint, make an important contribution to the person's pain. This study aims to understand how inflammation can lead to chronic pain that can persist long after the inflammation has resolved.

Why is this research important?

Previous research in mice and rats with arthritis has shown that blood-derived cells (cells created from or based on blood cells) play a role in arthritis pain even when joint swelling is very mild. The focus on blood-derived cells in pain mechanisms is a new area of research, and so is the idea that what maintains arthritis pain might be quite different from what causes swelling in the joint. This research will try to address this by aiming to understand the role of blood-derived cells in pain mechanisms further, which is crucial for the development of more effective therapies.

The researchers believe that blood-derived cells produce chemicals that increase pain sensitivity and have identified a way to stop such production. In addition, in arthritis, blood-derived cells do not produce enough chemicals that can reduce pain, and therefore the researchers plan to administer these chemicals to reduce pain. During this project, they will use a variety of methods to assess the activity of blood-derived cells in mice and rats with arthritis and determine the effects of this activity on the nerve cells that carry pain signals. They will then measure pain when specific activity in blood-derived cells has been either blocked or increased.

How will the findings benefit patients?

There are few studies of the specific mechanisms of rheumatoid arthritis pain. In particular, we do not fully understand the mechanisms that cause pain in absence of swelling. Because of this gap in knowledge, treatments that alleviate rheumatoid arthritis pain have yet to be developed. This project will aim to understand how inflammation can lead to chronic pain that can persist long after the inflammation has settled. This could lead to a better understanding of which specific treatments are most likely to reduce chronic pain, and when is the best time to deliver them. It could also lead to future clinical trials in people with rheumatoid arthritis.