Copine-6: A new clue to why showers hurt when we’re sunburnt
A recent study from an international team of researchers has identified a protein that influences how sensitive we are to heat-related pain, informing future approaches to pain treatment.
Published in the EMBO journal, the study is led by the Faculty’s Professor Nikita Gamper, a long-time researcher into the science of pain, alongside colleagues from Hebei Medical University in China.
The team has been exploring the role of a protein called Copine-6, also known as N-Copine, and discovered it plays a part in determining the range of temperatures we perceive to be painful.
By looking at how sensory nerve cells react, the research helps to explain why we feel more sensitive to heat in several everyday experiences. For example, why sunburn makes us more sensitive to warmth like a hot shower, or why drinking hot tea can feel painful when we have toothache.
“In many chronic pain conditions, we become very sensitive to warm temperatures,” explains Nikita Gamper, Professor of Neuroscience in the School of Biomedical Sciences and corresponding author of the study. “Our findings help to understand why.”
What the research has found
Image: A sample from the research showing that Copine-6 (in red) is abundantly present in sensory neurons
Unlike many pain studies that focus on how the brain processes pain signals, this research looks at what happens in the nerves themselves. The paper explains that the protein Copine-6 can be found in specific nerve cells known as dorsal root ganglion (DRG) neurons, that detect sensations like heat, cold and touch.
These neurons also contain an ion channel called TRPM3, which helps to detect painful heat.
“Copine-6 helps TPRM3 to get the surface of the nerve cell, where it can sense heat” says Professor Gamper. “Our research has indicated that when Copine-6 is removed or reduced, the nerve cells become less sensitive to painful heat.”
The Copine-6 protein was first flagged by an undergraduate student a few years ago as part of their final year project, when they were confined to desk-based research work due to the COVID pandemic. “This was a really important part of the puzzle and really laid the groundwork for the current study” says Professor Gamper.
Using a combination of molecular biology, imaging and animal behavioural testing, the teams of researchers have been able to show that reducing Copine-6 leads to a measurable decrease in heat sensitivity, without affecting responses to cold or pressure.
The paper also references other studies that support the role of TRPM3 in heat sensation and reinforces the significance of Copine-6 as a regulator of pain. Together, these findings help to reveal a new way that the body controls pain signals through our nerves.
Implications for treating pain
The discovery could open new possibilities for treating pain, particularly in instances where pain is related to heat hypersensitivity, such as inflammatory pain experienced by arthritis patients or pain related to nerve damage.
“We think we know the system of pain within the body well, but we don’t,” says Professor Gamper. “The devil is in the detail, and as long as we don’t know the details, we won’t be able to treat pain effectively.”
“We need to develop pain treatments that stay in the nerves. Opioids go into the brain, which can make you euphoric or sleepy, but pain medication could be much more effective if we can refocus it to the peripheral nervous system.”
Further information
The paper is published as: Yiting Gao, Shengxiang Yan, Zhongyang Zhang, Jieyao Zhang, Meng Yang, Shihab Shah, Sofia Figoli, Qi Jing, Haixia Gao, Nikita Gamper (2025) Copine-6 is a TRPM3 escort protein controlling the sensitivity of sensory neurons to noxious heat
This research was supported by the Wellcome Trust, the Medical Research Council, the European Union’s Horizon 2020 programme, and funding bodies including the Hebei Province Talent and Intelligence Introduction Project and the National Natural Science Foundation of China.
Top image: Adobe Stock
