Extracellular Vesicles Communication for Nociceptive Processing in Acute and Chronic Pain

Start date: 1 January 2025
End date: 1 January 2030
Funder: Medical Research Council (MRC)
Value: £1,158,255
Primary investigator: Prof Nikita Gamper
External co-investigators: Professor Marzia Malcangio, Wolfson Sensory, Pain and Regeneration Centre, King’s College London; Professor Mauro Perretti, William Harvey Research Institute, Queen Mary University of London, Eli Lilly

Project title

Description

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.

Moreover, 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 our understanding of the biology of pain, and acute pain can be managed well in the clinic. However, here we wish to understand what is responsible for pain to stay.

In previous studies, the Gamper lab uncovered sharing of ‘packaged information’ between pain nerves and other cells within the dorsal root ganglion’ (DRG) – a structure of pain cells outside the brain.

We 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 propose that there are hubs for such EVs communication in the DRG which regulate chronic pain and can be targeted to decrease pain sensitivity.

We believe that EV-mediated mechanisms can be exploited to regulate pain cell activity; this, in turn, 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 analgesics, e.g. opioids.

Research overview

In this project, we will characterise vesicles released by nerve cells and other cells residing in the DRG and identify those which may have escaped into the blood.

We will establish their ingredients and properties to define their role in pain mechanisms and diagnostics.

This objective will be achieved through four focused aims:

To map the direction of vesicle signals between pain nerves and other cells in the DRG.
To discover properties and composition of vesicles from specific cells.
To investigate short, mid and long-term effects of cell-specific vesicles and their components on pain cell activity.
To unveil 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 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 also 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 and pain management, thus having far-reaching benefits not only for the fundamental science but, ultimately, for individuals suffering from chronic pain conditions.

This grant is part of a wider collaborative government and industry investment totalling £3.5m.