Understanding the biological memory of chronic pain

Chronic pain is often doubly-distressing. For many individuals it not only hurts, but also doesn’t have a clear measurable cause. This can make it difficult to seek help and understanding for pain conditions from doctors, family or friends, and it can also be a barrier to receiving effective and timely treatment.

We know that people with chronic pain show abnormalities in how the brain processes sensory experiences from the outside world and from inside the body. Much research is therefore focused on identifying which brain pathways are disturbed and how to fix them.

Role of non-neuronal cells in chronic pain

Another cause of chronic pain is often overlooked, called dysfunctional tissue resident cells. For example, your ankle may look like it has healed after an injury because it is not swollen or show signs of inflammation. However, this does not mean that all the cells inside your ankle are healed. Immunologists have shown that immune and connective tissue cells in an injured area can be affected long-term and continue to release distress-signals. These might then be picked up by the sensory nervous system and be experienced as pain.

Our team is planning to investigate the role of these cells in chronic pain and how they communicate with nerves. At King’s College London, we have strong links between neuroscientists and immunologists, for example, we host a King’s and Wellcome Trust-funded training programme in Neuro-Immune Interactions.

Moreover, members of our National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre have used model systems to show that chronic pain is accompanied by long-lasting immune system dysfunction (see studies 1 & 2). Together with immunological collaborators (some of whom are part of Guy's and St Thomas' Biomedical Research Centre), we identified factors released by human fibroblasts which might affect nerves negatively.

1) 1 in 5 people suffer from chronic pain.

2) Our research shows that local cells in tissue play a role.

3) We plan to research the factors released by these cells that affect pain...

4) …and then develop and trial drugs that block these factors.

Future research and collaboration

This research is a first step to develop an interdisciplinary experimental medicine programme. We will use patient-derived immune and connective tissue cells to investigate which of the factors we identified cause most activity in human sensory neurons.

In collaboration with clinical colleagues, this work will examine a variety of conditions, including musculoskeletal and facial pain. We will work towards an early-stage clinical trial, blocking the most promising non-neuronal cell-derived factor in patients that we will carefully investigate for both their pain and immunological dysfunction.

Our overarching aim is to identify better pain interventions that treat the root cause of chronic pain locally in the body.

 

 

IMPACT AREAS:

Novel Diagnostics and Therapeutics