Scientists find that the body's warmth sensor is secretly a pain switch
University of Warwick scientists have found that a sensor in our nerve endings that detects warm temperatures also plays a direct role in switching on chronic pain signals, a discovery that could lead to better treatments for conditions that affect millions of people.
Chronic pain, including arthritis pain, affects over a third of UK adults. Current painkillers such as methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) work by damping down the immune system, which is overproducing inflammatory agents to cause the pain, but their relief is often short-lived, incomplete, and can leave patients more vulnerable to infection.
Researchers at Warwick's School of Life Sciences have found an alternative target for alleviating chronic pain - a channel called TRPM2. TRPM2 was previously known mainly as a ‘warmth sensor’ on sensory nerve endings, helping the body detect mild, non-painful, heat.
In the new work published in PNAS, the team discovered that TRPM2 has a second, more troubling job. They found that TRPM2 on sensory nerves is also a pain generator. Prostaglandin E2, a chemical released during inflammation, and autoantibodies, immune proteins produced by the body's own immune cells, both act directly on TRPM2 to switch on pain signals in nerve cells.
“We found that TRPM2 works like a convergent pain switch, taking very different immune and inflammatory signals and converting them into the electrical impulses that the brain reads as pain," said lead author, Dr Xuming Zhang, School of Life Sciences, University of Warwick. “These signals also switch TRPM2 on through completely unexpected routes, bypassing the cell's usual signalling pathways entirely.”
As a demonstration of its role in pain, mouse models with TRPM2 removed from nerve cells showed pain caused by prostaglandin E2 and autoantibodies was completely prevented. Chronic arthritis pain and nerve injury pain were also substantially reduced, even though the underlying immune and inflammatory response carried on largely as normal. This suggests TRPM2 is a separate, direct route to pain, working alongside inflammation rather than being caused by it.
Most strikingly, blocking TRPM2 with a drug injected into the joint completely reversed arthritis pain in mice, and the relief lasted two days after a single dose, without dampening the joint inflammation itself.
Dr Zhang continued: "What surprised us most was how completely and how long TRPM2 blockade relieved chronic arthritis pain. That points to TRPM2 as a genuinely promising drug target for treating chronic pain more effectively than current options allow."
The findings also raise an intriguing biological puzzle: how does a protein built to detect harmless warmth end up driving some of the body's most stubborn pain? Dr Zhang's team suggests different populations of TRPM2-carrying nerve cells may be responsible for each job, a question they hope to explore next.
ENDS
Notes to Editors
The research was led by co-first authors Dr. Mujahid Alizada, Linda Varghese and Jinquan Yang and was funded by the Medical Research Council (MRC), the Biotechnology and Biological Sciences Research Council (BBSRC) and Versus Arthritis UK, and is published in PNAS, DOI: 10.1073/pnas.2532289123.
For more information please contact:
Matt Higgs, PhD | Media & Communications Manager (Warwick Press Office)
Email: Matt.Higgs@warwick.ac.uk | Phone: +44(0)7880 175403
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17 September 2026