Searching for the source of chronic pain

One in five adults in Sweden suffers from chronic pain. This causes not only great suffering to the individual, but also takes its toll on society in the form of hospital costs, sick leave and loss of productivity. This is an issue that does not receive enough attention, believes Camilla Svensson, pain researcher at Karolinska Institutet and a Wallenberg Academy Fellow.

Camilla Svensson

Professor in Cellular and Molecular Pain Physiology

Wallenberg Academy Fellow/Wallenberg Scholar

University:
Karolinska Institutet

Research field:
Molecular pain research

Chronic pain costs more than cancer, diabetes and cardio-vascular disease combined, according to a recent U.S. study. Over 40 percent of all long-term sick leaves are essentially due to pain.

“Chronic pain is a major problem facing society. If we can treat pain effectively, then many people on sick leave may be able to resume active lives,” says Camilla.

She has seen at close quarters how pain reduces quality of life. Her own father injured his shoulder some fifteen years ago, and has been living with chronic pain ever since. He had always led a very active life and kept fit, but was forced into a completely different mindset.

“He describes the pain as like walking around with a backpack that you can’t take off. The weight is a constant distraction. There are drugs that work in the short term, but if you use them for too long, they stop working; and raising the dose brings the risk of side-effects.”

Hoping for better treatments

To experience constant pain is to suffer, and this has spurred Camilla to try to understand the molecular mechanisms of pain in order to develop better treatments. Her focus is on joint pain and the relationship between inflammation and pain, particularly in rheumatoid arthritis and arthrosis.

“It was while I was working on my thesis in California that I realized that pain is an element in a huge number of diseases, and that pain itself can become a disease. For instance, we can see that people suffering from chronic pain are more susceptible to depression and sleep badly, factors that in themselves impact the immune system, lowering resistance to infection.”

While other young researchers concentrated on known diseases such as HIV, diabetes and cancer, Camilla developed a growing interest in the problems of pain. She found that pain researchers and rheumatologists communicated surprisingly little with one another, and that they used quite different model systems.

“This was an obvious failing, and I saw the role I could play in bridging the gap. So when I set up my own lab my aim was to characterize and evaluate two of the model systems from a pain perspective. This had never been done before.”

She calls it conducting disease-centered pain research: beginning with the disease and finding out all relevant facts about it, before transferring that knowledge to neuroscience and pharmacology from a pain perspective. And the new approach has already yielded new and somewhat surprising information.

Pain occurs before inflammation

Researchers had believed that inflammation itself was the root of the pain. But Camilla’s research shows that pain can occur at an earlier stage of a disease. Even before the disease breaks out, antibodies against proteins can be found in the joints, and those antibodies may be what trigger pain signals.

Pain without inflammation could therefore explain why nearly half of all patients on medication that has reduced inflammation in their joints still report joint pain. Camilla will now continue detailed study of the role played by antibodies in pain.

“For me, the most important thing is to identify new approaches to inhibiting pain signals. Not to turn them off altogether, but to normalize nerve activity. It must still be possible to put your hand on a hot stove and feel sharp pain, while no longer suffering from aching and disruptive pain, which ultimately becomes an abnormal condition.”

“It confirms that my line of research and the areas on which we are concentrating have been recognized as important. The award is a privilege and a responsibility. Now it is time to show what I can do, and I like challenges. Having lived in the US for many years, I am also delighted to have the opportunity to get to know other researchers in Sweden working at the same level. The leadership program that follows with the award is also important.”

If the role of antibodies is as researchers believe, the next challenge will be to find out whether new drugs can be used to target the neurons to which the antibodies bind.

“If our wildest fantasies come true, I think that in five years’ time we will have identified antibodies as pain-blocking molecules.”

Overlooked cells amplify pain

There are several lines of research. When pain signals from nerve cells in a damaged joint rush to the brain they meet up with other pain neurons in the spinal cord. This can amplify the pain. Contributing to this are support cells called glial cells, whose role in pain was long overlooked by researchers.

“Our model systems show that glial cells morph into larger cell bodies with numerous branched protrusions. They act aggressively and become more active by releasing substances that can amplify pain signals.”

Next, Camilla wants to find out what activates glial cells when joints become inflamed, what substances they release, and whether they play the same role in humans as in the animal models. Perhaps glial cells can also serve as a target for future pain relief.

“As a student I envisioned myself as a researcher surrounded by test tubes, wearing a white coat, goggles and protective gloves. That doesn’t happen much nowadays, but it’s a great feeling being the one who coordinates everything and puts all the pieces together. I derive enormous motivation from the fact that our work straddles the fields of basic research and clinical benefits.”

Text Nils Johan Tjärnlund
Translation Maxwell Arding
Photo Magnus Bergström