Supporting those with fibromyalgia pain
Resistance and challenges have not stopped Professor Eva Kosek. On the contrary, she has actively swam against the tide. Thanks to her research, there has been an increased understanding of the pain disorder fibromyalgia – and patients today encounter less suspicion.
Text: Cecilia Odlind, first published in Swedish in Medicinsk Vetenskap, No 1/2019.
“Why do you research something that doesn’t exist?” Eva Kosek was often asked that question at the beginning of her professional career. In the 1990s, fibromyalgia was a controversial diagnosis. It was dismissed as a catch-all diagnosis for women in particular who had a lot of pain for unclear reasons.
“But I like to swim against the tide. I figured that if no one else cares about these patients, at least I should,” she says.
As a pain doctor, she heard similar stories from many different patients. Typical symptoms included increased sensitivity to pain: They said that things that would normally not hurt, such as a cold draft from a window or when someone hugged them a little too hard, caused severe pain.
“It became clear to me that this was not just about whining – it was a real problem.”
The whole idea of pain is to protect us from injury or keep us resting so that the body can heal. Signals go from the body to the brain where new signals are sent down the spinal cord back out into the body. These can weaken or strengthen the pain.
When we move our body
Pain inhibition can for example begin when we move our body. Similarly, pain in one part of the body can lead to reduced pain sensitivity in other parts of the body. But this pain inhibition did not seem to work in patients with fibromyalgia. This made Eva Kosek consider whether the problem had to do with the regulation of pain in the central nervous system rather than pain receptors in the muscles. And this turned out to be the case. In 1997, her research team and a German research team – more or less simultaneously and independently of each other – were able to show that fibromyalgia patients have disturbances in their endogenous pain inhibitory systems.
“The filtering out of pain signals that occurs, for example, in healthy people does not work in the patients. To put it simply, you can say that the filter has a wider mesh, letting more pain signals reach the brain,” says Eva Kosek.
This gave us a new understanding of what the approximately 200,000 Swedes diagnosed with fibromyalgia were suffering from. Could this also apply to other pain disorders? To answer this question, Eva Kosek’s research team conducted trials on patients with the joint disease osteoarthritis. By restricting the oxygen supply to the arm with a blood pressure cuff, they provoked a severe pain in one group of patients and one group of healthy test subjects. They tested the pain sensitivity to pressure on the thigh before, during and after the pain provocation. In the healthy subjects, the thigh pain was clearly inhibited by the arm pain, while this was not the case with the osteoarthritis patients. The results were published in a scientific article in 2000.
“But then talk about this issue died down among pain researchers. I was waiting for someone to do a similar study and show the same thing, but nothing happened. That made me really, really nervous. I didn't understand why and started wondering if our findings were correct. A fundamental assertion within science is that one single study does not prove anything, the results must be able to be reproduced, preferably multiple times and by other researchers,” says Eva Kosek.
It took ten years for the findings to pick up speed again, with a number of new studies confirming what Eva Kosek’s research team had observed. Since then, the field has developed significantly. Today, this is established knowledge.
Exactly what happens at the cell level is not really known. But the process has been mapped out: It starts with a localised pain in the body, which in some individuals exhausts the pain-inhibiting systems. This causes increased pain signalling and higher pain intensity.
“It can be likened to a meadow where a path has appeared due to people walking through it. It becomes easier and easier to walk that particular path. In the same way, two nerve cells that often have contact with each other will become better and better at communicating. Ultimately, this can also lead to more surrounding nerve cells being activated, which can result in pain radiating to a larger area around the place where the pain arose,” says Eva Kosek.
Recently, her research team has been interested in inflammatory processes in pain patients. They have noted that osteoarthritis patients have elevated levels of inflammatory substances, cytokines, where they have their osteoarthritis, such as the knee. But inflammation can also be observed in the spinal fluid.
“Inflammation in the body appears to be mirrored by an inflammation of the central nervous system. But interestingly, the effects can be different. The inflammation of the joints proved to be associated with more symptoms, such as pain, whereas the inflammation of the brain was conversely associated with less symptoms,” says Eva Kosek.
Central nervous system
Depending on the type of inflammation in the central nervous system, it may be associated with a decrease or an increase in symptoms. Using the positron emission tomography (PET, a form of brain imaging technology), the research team has been able to show that a certain type of glial cell with immunological competence is activated and likely responsible for central nervous system inflammation in patients with fibromyalgia. The more pronounced the glial cell activation in a certain part of the patients’ brain, the more fatigued they were.
“Finding ways to support the positive effects of glial cells and dampen the negative ones would unlock completely new treatment options,” she says.
The findings regarding brain inflammation in patients with fibromyalgia have brought great medial attention. The fact that the study can demonstrate objective abnormalities in the brain of these patients can hopefully reduce the distrust that many people encounter, believes Eva Kosek.
“Their situation is still difficult, but it is much better than when I started in the field. There has been a tremendous increase in awareness which has led to us, in addition to nociceptive pain and neuropathic pain, now talking about a third form of pain, nociplastic pain, which is due to disturbances in the pain regulation system,” she says.
Thanks to this new knowledge, several new drugs have also been developed which are directed towards the pain regulation system. There are also improved training programmes and psychological treatment methods available. However, the fibromyalgia diagnosis is still not completely clinically established.
Stubborn, optimistic and proactive
“I'm still an optimist. Since nociplastic pain is now defined, we are starting to talk about pain as an illness in and of itself. Just like you have high blood pressure as a symptom of, for example, kidney disease or have high blood pressure itself due to disturbances in blood pressure regulation, you can also have pain as a symptom of an injury or pain as a result of disturbances in the pain regulation system, that is, as an illness in its own right,” says Eva Kosek.
Research in general, and research on a criticised subject in particular, seems to suit Eva Kosek for several reasons. She describes herself as stubborn, optimistic and proactive.
“As a researcher, you are scrutinised hard by colleagues and financiers, and rightly so. It’s important to be able to accept justified criticism, but at the same time not let yourself be put down too much, especially if you are testing new ideas,” she says.
Eva Kosek also emphasises the importance of good judgment.
“In the research, you have to draw the right conclusions from your results. You need to clearly separate hypotheses or ideas from what we presently know.”
She is not deterred by the difficulty of research.
“Difficult is fun. Once you know the answer to a question, then it’s easy and may seem obvious. But before you know the answer, it’s not as easy. Research is about generating new knowledge and this means making your way through fog to the best of your ability. Once it has dissipated, it’s time to move on. The way forward will always be shrouded in fog,” says Eva Kosek.
Name: Eva Kosek.
Title: Professor of Clinical Pain Research at the Department of Clinical Neuroscience, Karolinska Institutet.
Family: Husband and two grown children.
What I do to relax: Reading fiction, slalom skiing, dancing, outdoor life. I have also had guinea pigs for 22 years. Right now there are six of them living in open cages in the kitchen. They wander freely in their enclosure and stay there. It’s relaxing to observe how they live their lives.
Eva Kosek on …
…pain being invisible
Many people who suffer from pain are told that they “look so healthy”. The condition is often associated with being overly dramatic, but I think that is extremely unfair. Many people struggle on their own for a long time with little support from society.
More women suffer from pain, but we don’t know why. Serotonin, which has to do with pain regulation in the brain and which is depleted during stress, is replenished faster in men. One hypothesis is that this makes women more sensitive to pain and anxiety.
Of all the studies we have done, it has often been most difficult to publish those that, in my opinion, are most interesting and innovative. When you walk a well-trodden path, you encounter less resistance than when you beat new paths.
…pain patients struggling to get help
Today, everything is expected to be quick, easy to understand and cheap. But pain takes time to investigate and treat, and it often depends on complex mechanisms and requires collaboration in healthcare, which makes it expensive. Too few patients get access to the right kind of help.