New approach to protein identification offers promise for better understanding of pain

An innovative screening technique, developed by researchers at the University of Leeds, has successfully identified new molecular cold receptors.

This cutting-edge new approach, developed as part of a project to improve understanding of how the nervous system detects and responds to pain and temperature, is based on the idea of harnessing artificial cellular evolution to create a diverse library of cells through random mutations. 

This forces the emergence of rare cellular traits, and allows researchers to identify the proteins responsible for them.  

A variation of the approach has been used in cancer gene discovery studies, however, scientists in the School of Biomedical Sciences have pioneered an advanced platform to extend the reach of this high-yield strategy and allow identification of proteins involved in a broad range of biological fields, such as pain.      

This is an important first step in our efforts to better understand the molecular mechanisms of pain, but what’s particularly exciting is that this unbiased screening platform has the potential to identify a variety of genes which play roles in other conditions and diseases. 

Understanding pain receptors 

A new project, funded by Wellcome and which is being led by Dr Viktor Lukacs in collaboration with Professor Nikita Gamper, Dr Beatrice Maria Filippi and Dr Jamie Johnston, in the School of Biomedical Sciences, will take this discovery one step further by identifying the necessary and sufficient gene composition of the newly discovered receptors, test their expression in various organs and cells, and uncover their potential physiological role in temperature detection, pain, and metabolic control. 

Our goal is to identify new potential drug targets in the nervous system which could lead to more effective and safe treatments for chronic pain.

Chronic pain 

1 in 3 people in the UK experience chronic pain, a debilitating condition with serious negative impact on quality of life. 

Treatments such as opioid medications, which are effective in alleviating chronic pain, can be very dangerous to use, and therefore often restricted. The efficiency of these medications declines over time, leading to increased dosing and potentially, addiction. 

The use of these medications also prevents patients from performing normal daily tasks, such as driving. New solutions to this highly prevalent problem are therefore urgently needed. 

To discover new and safer pain management strategies, we must first better understand the molecules that are involved in generating the initial signal that later becomes the feeling of touch and pain. 

The science behind the way we feel temperature 

Understanding the role of temperature in relation to pain is an important piece of the puzzle when finding new treatments for chronic pain.

This is because pain is governed by similar drivers to temperature called sensory nerves, whose long processes supply the rich tapestry of nerve endings in our skin and internal organs. 

These nerve endings carry a host of different specialised molecular sensors called receptors, tuned to respond to temperature changes in a certain range. 

Scientists have already discovered several of these receptors, particularly those that sense heat. However, the way we detect very cold temperatures is much less well understood. 

The effects of cold 

Cold can affect our bodies in a myriad of ways. For example, cooling injuries or inflammation often helps to reduce associated pain. 

However, in some patients, cold induces the opposite effect, triggering severely painful episodes. We also know that cooling increases the body’s metabolism, and triggers shivering- and non-shivering heat generation beyond a certain point. How all these effects come about on a molecular level is mostly unknown. 

Understanding them promises a safer avenue towards the management of chronic pain, and potentially many other conditions as well.

Keep updated about the project 

To keep updated about the project, visit Lukacs Lab website. You can also reach out to Dr Lukacs if you’d like further information or to discuss collaboration opportunities.