Unlocking the mystery of fibromyalgia

Understanding the biological basis for fibromyalgia could help transform treatment options for patients.

Fibromyalgia (FMS) is a chronic pain condition affecting more than 2% of the UK population, characterised by widespread pain, fatigue and brain fog.

Like many other chronic pain conditions, it is often considered a “functional neurological disorder” but current treatments such as cognitive behavioural therapy and physical exercise have limited efficacy.

In a breakthrough study, our researchers have shown that fibromyalgia may be a disease of the immune system, which could transform how the condition is viewed and help lead to new and improved treatments.

Challenging convention

Dr Andreas Goebel, Director of the University’s Pain Research Institute and an Honorary Consultant in Pain Medicine at Walton Centre NHS Foundation Trust tells us “Fibromyalgia does not cause tissue destruction but is hugely debilitating and expensive - many people can’t function in their daily lives and can’t work.

"Like other unexplained chronic pains, fibromyalgia has often been thought of as psychological, with many patients told their pain symptoms are ‘all in their head.'

That a patient’s own antibodies could cause these symptoms and that this could be tested using ‘passive transfer’ experiments were ideas I first developed 20 years ago in Liverpool while researching complex regional pain syndrome (CRPS). These ideas went on to lay the groundwork for this landmark fibromyalgia study.”

Collaborative effort

Dr Goebel was part of a collaborative research team – involving Kings College London and the Karolinska Institute – that showed that many of the symptoms in fibromyalgia are caused by antibodies that increase the activity of pain-sensing nerves throughout the body.

Fibromyalgia patients from the Walton Centre’s Pain Management Programme donated blood for the project so that their antibodies could be extracted.

The researchers injected mice with these antibodies and observed that they rapidly developed an increased sensitivity to pressure and cold, as well as displaying reduced movement grip strength. In contrast, mice that were injected with antibodies from healthy people were unaffected, demonstrating that patient antibodies cause, or at least are a major contributor to the disease.

Furthermore, the mice injected with fibromyalgia antibodies recovered after a few weeks, when antibodies had been cleared from their system. This suggests that therapies which reduce antibody levels in patients are likely to be effective treatments. Such therapies are already available and are used to treat other disorders that are caused by autoantibodies.

Paradigm shift

Dr Goebel said, “Our findings require replication by others, but if the results are reproduced then the implications are profound. We have now, for the first time, a valid, mechanism-driven disease model for FMS that should pave the way for the development of new diagnostic tests and immune therapies.

“This is an exciting time for the fibromyalgia community as it opens up the possibility that one or more of the many treatment options available for immune-mediated disease could have a real impact in fibromyalgia too.

"Our work could also have potential for fundamental, disruptive developments in the understanding and treatment of other ‘unexplained’ symptom-based disorders, such as long Covid.”

Since its publication in July 2021, the study has received a huge amount of interest from fibromyalgia patients, clinicians and researchers, as well as industry and the wider media. In a mark of its impact, the study was chosen by leading scientists as one of the Guardian’s Top 10 Science Stories of 2021.

Health inequalities

Dr Goebel also believes that the findings could help explain some of the known health inequalities seen in fibromyalgia, saying, “Stressful experiences are likely involved in triggering the immune response that we discovered in our study, although not in every patient. We know that deprivation can cause stress and there will also be genetic risk factors. We need to conduct research to understand the role of stressful events and learn how to prevent their effects where possible.”

Liverpool expertise

Liverpool has a long and established history of a pain service and pain research. The University’s Pain Research Institute brings together academic and clinical expertise from across the region to support research into the causes and best treatments of human chronic pain.

Supported by the Pain Relief Foundation, the institute collaborates closely with the Walton Centre NHS Foundation Trust, which runs one of the largest Pain Management Programmes and Pain Services in the UK.