Understanding the biology of chronic pain

Professor Nikita Gamper explains how a new £1.2m programme will support new knowledge about chronic pain which could potentially benefit billions of people.

Chronic pain is a distressing condition that, unlike acute pain, remains poorly treated by currently available medicines. Chronic pain affects over a third of the world population and costs the economy billions.  

Since prevalence of chronic pain increases with age, the economic burden of pain will rise due to the ageing population of our society.  

Scientists have made remarkable progress in understanding the biology of pain, and acute pain can be managed well in the clinic, but there are still big gaps in knowledge, such as how and why pain persists. 

The dorsal root ganglion 

In recent studies, we found evidence to suggest pain cells outside the brain in a structure called the ‘dorsal root ganglion’ (DRG) may cause pain to stay. 

Using rodent models of chronic pain, we made breakthrough discoveries, uncovering sharing of ‘packaged information’ between pain nerves and other cells within the DRG.

This information exchange at the DRG can control pain signals before they reach the spinal cord, on their way to the brain, where pain is felt. 

We also discovered that there are miniature capsules called ‘extracellular vesicles’ (EVs) that shuttle from one cell to the other within the DRG and are also able to escape into the blood.  

We think that there may be hubs for such EVs communication in the DRG which regulate chronic pain and can be targeted to decrease pain sensitivity, and that EV-mediated mechanisms can be exploited to regulate pain cell activity.

This may give rise to novel approaches to both treating chronic pain and finding diagnostic markers for such pains. 

The fact that DRGs are outside the brain offers additional benefits for the development of targeted therapies which are devoid of many unwanted side effects, notoriously associated with current painkillers, such as opioids.

Defining the role of vesicles in pain and diagnostics

This new project, funded by the Medical Research Council and Eli Lilly, will bring together researchers in the UK and industry to study this in more detail.

Characterising vesicles released by nerve cells and other cells residing in the DRG, and identifying those which may have escaped into the blood, will lead to greater understanding of their role in pain mechanisms and diagnostics. 

We’ll do this by: 

• mapping the direction of vesicle signals between pain nerves and other cells in the DRG. 
• discovering properties and composition of vesicles from specific cells. 
• investigating short, mid- and long-term effects of cell-specific vesicles and their components on pain cell activity. 
• Unveiling how vesicle communication changes in chronic pain conditions, identify vesicle-associated diagnostic markers of chronic pain and explore innovative vesicle-based therapeutic approaches. 

We will use a variety of methods to characterise DRG-derived vesicles in animal models and in blood samples obtained from people with chronic pain.  

We will also determine the effect of such vesicles on the nerve cells that carry pain signals and measure readouts of pain when specific EV-mediated mechanisms have been blocked.

In both animal and human blood samples, we will assess whether vesicles are potential biomarkers of neuropathic pain. 

Our research will bring novel understanding of chronic pain mechanisms and will shape innovative approaches for analgesia (pain relievers) and pain management, thus having far-reaching benefits not only for the fundamental science but, ultimately, for individuals suffering from chronic pain conditions. 

About the project

The programme is led by Professor Nikita Gamper (University of Leeds) and co-led by Professor Marzia Malcangio (Wolfson Sensory, Pain and Regeneration Centre, King’s College London) and Professor Mauro Perretti (William Harvey Research Institute, Queen Mary University of London) in partnership with Eli Lilly. 

You can keep updated about the project by visiting Extracellular Vesicles Communication for Nociceptive Processing in Acute and Chronic Pain.