Pain not just a symptom

About 30% of patients with back pain or arthritic knee pain who undergo surgery are not pain-free afterwards. This also applies to patients with rheumatism.

PAIN

NOT UST A SYMPTOM

Pain is often seen as a symptom, but it can be a disease in itself which requires treatment. One example is fibromyalgia, which mainly affects women. Professor Eva Kosek has extensive experience in pain research and has now returned to Uppsala, where 40 years ago she studied medicine.

text ANNICA HULTH photo GETTY IMAGES, MIKAEL WALLERSTEDT

Today, pain is the second most common cause of sick leave in Sweden, after mental illness. Pain is often considered a symptom that disappears once its underlying cause is treated, for example, by knee surgery or treatment for rheumatism. But it is not always that simple.

“If you have a long-term pain condition where pain is initially a symptom, it can happen that after the nervous system has been bombarded by pain signals for a long time, the functioning of the nervous system changes. It starts to amplify the pain signals, like a loudspeaker where you turn up the volume. In some cases, it seems to be irreversible," says Eva Kosek.

She is a doctor at Uppsala University Hospital’s pain clinic and leads two research groups, one at Uppsala University and one at Karolinska Institutet.

ABOUT 30% OF PATIENTS with back pain or arthritic knee pain who undergo surgery are not pain-free afterwards. This also applies to patients with rheumatism. For 20–30%, the troublesome pain persists despite successful treatment of the infl ammation.

This type of pain is called nociplastic pain. One example is fi bromyalgia, a whole-body pain that mainly affects women. Using experiments in which pain stimulation was administered to subjects who rated their own pain, researchers have developed response curves. They also use magnetic resonance imaging to study the brain’s pain response.

“On the one hand, we have seen that people with fi bromyalgia are much more sensitive to all types of pain stimuli. On the other hand, we can see that, during pain stimulation, they do not activate their pain modulation systems in the normal way. We have been able to pinpoint the location in the brain of this dysfunction as well as how it is affected by, for example, expectations."

Eva Kosek is a doctor at Uppsala University Hospital’s pain clinic.

RESEARCHERS ARE ALSO studying how the immune system and the nervous system interact, by looking for different biomarkers in blood and cerebrospinal fl uid. For example, people with pain have been found to have increased levels of cytokines, proinfl ammatory substances, in their cerebrospinal fl uid.

In fi bromyalgia patients, they have also observed an activation of the brain's immunocompetent cells. These cells trigger the immune system, suggesting that something is happening in the interaction between the immune system and the nervous system.

Another line of research, which has received much international attention, is antibodies in people with fi bromyalgia.

“In collaboration with Camilla Svensson, professor at the Department of Physiology and Pharmacology at KI, we have extracted antibodies from blood from patients with fi bromyalgia and injected them into mice," says Kosek.

The researchers have found that the antibodies bind to a specifi c type of cell, known as satellite glial cells, which are activated. These satellite glial cells surround the cell bodies of the nerve cells and probably release substances that affect the nerve cells and amplify pain signalling.

THE FINDINGS HAVE ATTRACTED considerable international interest. Not least, UK newspaper The Guardian named the study one of 2021's ten most important scientifi c discoveries. Kosek sees big opportunities ahead.

“Should we succeed in this, we could have diagnostic methods for some severer forms of fi bromyalgia. Then you could select patients with lots of these antibodies and offer currently available immunomodulatory therapy. Ultimately, entirely new biologicals could be developed specifi cally for fi bromyalgia.”

A lack of belief on the part of GPs remains a serious problem, especially for fi bromyalgia patients, but also for other sufferers from long-term pain. Kosek therefore works extensively to spread information. She led the working group of the International Association for the Study of Pain that introduced the term ‘nociplastic pain’, and she is looking forward to the new global diagnostic codes in the International Classifi cation of Diseases (ICD 11), which will soon be in use.

“Pain has fi nally been given its own chapter, using the term ‘primary pain’ for pain as a disease. This is a direct refl ection of our own research and that of others.". ●