Nearly one in five people in Sweden suffer from chronic pain that lowers their quality of life. Pain is a component of many diseases, but can also be a disease itself, explains Svensson, who is a professor and pain researcher at Karolinska Institutet:

“Many people with chronic pain are susceptible to depression and poor sleep quality, both of which in themselves weaken the immune system and leave patients less protection against infections.”

Chronic pain also impacts society by adding to the costs of health care and sick leave. Yet pain has long been overshadowed by other health issues.

“But the situation has improved somewhat in recent years – pain receives more media attention, and more research funding.”

Research initiatives have enabled scientists to gain an idea of the mechanisms underlying pain. It used to be thought that inflammation itself was the underlying cause of pain. But Svensson’s research has shown that pain can occur in diseases before inflammation appears, and antibodies are present in the joints even before onset of disease. These antibodies can trigger pain signals.

“Our hypothesis has long been that antibodies play an important role in diseases, and now we have succeeded in linking antibodies to the symptoms of fibromyalgia.”

New insights on fibromyalgia

Diagnosis of fibromyalgia only became approved in 1990. Common symptoms include generalized sensitivity and pain, fatigue that is not helped by rest, and disturbed sleep. It’s estimated that two to four percent of the population suffer from fibromyalgia, and women are more likely than men to be affected.

Svensson and her team posed the question of whether there is an autoimmune component to the development of fibromyalgia. To find out, they extracted antibodies from patients with fibromyalgia and transferred them into mice. This is a labor-intensive project that has been made possible by funding from Knut and Alice Wallenberg Foundation.

“The support of Knut and Alice Wallenberg Foundation has enabled me to commit to high-risk projects. Research on antibodies takes a long time. Long-term funding with the possibility of renewal provides security. The Fellow and Scholar schemes also give me access to a network that has led to a number of collaborative projects.”

The research shows that mice with antibodies from fibromyalgia patients exhibit lower pain thresholds and experience widespread pain, just like that experienced by the fibromyalgia patients the antibodies came from.

“One diagnostic criterion is that a patient should have tenderness in four of five defined areas. We can see this in the mice.”

But it is not just the pain itself that is transferred via the antibodies. An in-depth behavioral analysis revealed that mice with the fibromyalgia antibodies move around less, lose muscle strength, and also show disturbed sleep patterns.

“We can identify numerous symptoms that are transferred via antibodies from fibromyalgia sufferers to the mice. From this we can infer that antibodies impact multiple areas of normal physiology, which is a very important discovery.”

The researchers have also found that antibodies accumulate in an area of nervous system tissue in mice. There they bind to a specific cell that wraps around the cell body of neurons that contain pain sensing receptors (nociceptors). Several studies suggest that these cells may affect the sensitivity of nociceptors, or in other words – cause pain.

“Perhaps the most important discovery we’ve made is that antibodies from fibromyalgia sufferers bind to exactly the same structure in human tissue as well.”

Better therapies 

Hopefully, the next step will be to identify the target molecule to which the antibodies bind. The goal is to develop better treatments. One possibility is to make use of existing drugs that either impact the production or effect of antibodies but that are not currently approved for treatment of fibromyalgia.

“We’ve screened blood samples from a large number of patients, and have realized that antibodies alone do not explain the disease. Our data indicate that between forty and fifty percent of people with the disease have ‘problem antibodies’ of this kind.”

These new insights may also enable researchers to develop diagnostic tools for fibromyalgia, which are currently lacking.

“At present there are no blood tests or physical tests we can use. Current diagnosis is based on the patient’s own account of their situation.”

More knowledge about fundamental mechanisms will also make it easier to gain an idea of potential causes of the disease. Svensson has colleagues across the world who are researching a broad range of topics, from gut microbiota and genetics to traumas such as accidents and extreme stress, which patients have experienced and documented.

“It’s essential to understand what causes these individuals to begin to produce pain-inducing antibodies. It’s also vital to find out what the antibodies bind to, which is what we’re focusing on at the moment. That piece of the puzzle will give us important information about how the antibodies trigger increased activity in the nociceptors. This will in turn create a basis for identifying additional ways of alleviating or preventing the pain.”

Svensson is studying a number of painful conditions, including rheumatoid arthritis and osteoarthritis. She enjoys working in the border zone between basic science research and translational research that will directly benefit patients in the clinic.

“It’s really motivating, especially when we get to hear the patients’ own accounts. But we are basic researchers, and although progress is being made all the time, there is a long road ahead before our findings can be put to practical use.”

Text Nils Johan Tjärnlund
Translation Maxwell Arding
Photo Magnus Bergström