We have identified a mechanism that shows how JAK inhibitors are more effective than other classes of anti-inflammatory drugs at relieving pain. They not only treat inflammation – and so indirectly reduce pain by reducing the effect that inflammation has on nerves – but they also act on nerves directly by silencing the nerves that are in the joint.
Dr Franziska Denk, Reader in Neuroscience at King's and co-senior author on the paper
23 May 2025
Research sheds light on how rheumatoid arthritis drug relieves pain
New research from King’s College London has found how a type of anti-inflammatory drug works to relieve pain in rheumatoid arthritis. The findings could pave the way for developing better painkillers for a range of inflammatory conditions.
Janus Kinase (JAK) inhibitors are a type of anti-inflammatory drug that are widely used to treat inflammatory conditions, such as rheumatoid arthritis – an auto-immune disease where the immune system mistakenly attacks the cells that line the joints, causing the joints to swell, and become stiff and painful.
As well as reducing inflammation, research suggests that JAK inhibitors are more effective than other anti-inflammatory drugs at relieving pain in rheumatoid arthritis, but how they do this is not fully understood.
A new study, published in JCI Insight, has shed light on how JAK inhibitors work to reduce pain, showing that they have a dual mode of action – reducing inflammation as well as blocking signals to the nerve cells that trigger our bodies to feel pain.
Researchers looked at samples of fluid from the inflamed joints of women with rheumatoid arthritis, collected from Guy’s and St Thomas’ NHS Foundation Trust. The joint fluid samples contained higher levels of multiple signalling molecules that cause inflammation compared to blood samples from the same patient or from healthy donors. Some of these signalling molecules are also known to activate nerve cells.
Using human stem cells, the team grew nerve cells responsible for detecting pain (known as sensory neurons) in the lab. When they added the joint fluid samples from rheumatoid arthritis patients to the nerve cells, the signalling molecules interacted with the nerve cells, activating them. One signalling molecule in particular, called LIF, was found to activate the nerve cells.
The team found that the nerve-activating effects of the joint fluid could be blocked when they added a JAK inhibitor. The JAK inhibitor stopped the nerve cells from becoming activated by the joint fluid.
The laboratory work was conducted, in large part, by Yuening Li, a student on the Wellcome Neuro-Immune Interactions in Health & Disease PhD Programme at King’s College London.
Rheumatoid arthritis affects about 1% of the UK population and is more common in women. JAK inhibitors are available on the NHS for adults with moderate to severe rheumatoid arthritis who can’t take other kinds of drugs; however, there are safety risks associated with taking JAK inhibitors.
Having identified the signalling molecules in inflamed joints that activate nerve cells, the findings from the study could pave the way for the development of more effective painkillers, for a range of inflammatory conditions, that target these molecules.
With this work, we aim to address a major unmet need for patients with rheumatoid arthritis, namely what drives pain and how can we regulate it. This work was a great example of team science and collaboration between PhD students, postdocs, research assistants, neuroscientists, immunologists, inflammation biologists, rheumatologists – and was inspired by conversations with patients.
Professor Leonie Taams, Professor of Immune Regulation & Inflammation at King’s and co-senior author of the paper
The team is now looking at the different signalling molecules involved in inflammation and nerve cell activation in rheumatoid arthritis, to see which would make the most effective targets for drug development.
The study was funded by Wellcome as part of the Wellcome Neuro-Immune Interactions in Health & Disease PhD Programme at King’s College London and by a Wellcome collaborative award.
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Head of the School of Immunology & Microbial Sciences
Reader in Neuroscience