Neuroimmune interactions in chronic pain
To be able to make the right decisions and protect ourselves from danger, we need to get information regarding what happens in our environment, as well as the status of our own body. For this purpose, our two protective systems, the nervous and the immune system constantly interact and communicate through the release of different substances, including the traditional transmitter substances as well as cytokines, small proteins important for cell-to-cell signaling. Cytokines can be released by nerve- and/or immunocompetent cells during pain, stress, inflammation and infections. They influence the signaling in pain pathways and have immunoregulatory functions. Cytokines can activate glia, the immunocompetent cells of the central nervous system. In animal studies, activated glia have been reported to cause increased pain sensitivity, reduced analgesic (pain relieving) effects of opioids (i.e., opioid tolerance) and are likely to mediate the fatigue and sickness response seen during infections, inflammation and various pain conditions. Activated glia also release cytokines that interact with other glia cells and with neurons. The situation is further complicated by the fact that certain cytokines have pain promoting and pro-inflammatory effects while others can be analgesic and anti-inflammatory. Compared to controls, we have previously documented elevated cytokine concaentrations in the cerebrospinal fluid of patients with fibromyalgia, lumbar disc herniation, osteoarthritis, and rheumatoid arthritis, however, different cytokine profiles were seen in the various pain conditions indicating disease specific forms of neuroinflammation. In addition, we demonstrated glia cell activation in fibromyalgia patients compared to healthy controls, but this was not seen in patients suffering from rheumatoid arthritis, indicating differences in glia activation between the two conditions. Our current research deals with unraveling how different cytokines, inflammatory markers, metabolites, lipids and antibodies contribute to various aspects of chronic pain in humans. More specifically, we plan to study a) why approximately 20-30% of patients with rheumatoid arthritis develop a chronic, nociplastic, fibromyalgia-like pain despite successful anti-inflammatory treatment and b) the importance of immune mechanisms, including specific antibodies for pain development in subgroups of fibromyalgia patients and c) the role of lipids and small proteins for pain in osteoarthritis, disc degenerative disease and disc herniation. The overreaching aim is to understand how the nervous and the immune systems interact in causing chronic pain in order to facilitate the development of new treatment strategies. The projects are collaborations between the Department of Surgical Sciences and Department of Medical Sciences at Uppsala University, Department of Clinical Neuroscience and Department of Physiology and Pharmacology at Karolinska Institutet, Stockholm, the Pain Center and the Rheumatology Clinic, Uppsala University Hospital, the Rehabilitation University Clinic at Danderyds Hospital in Stockholm and Stockholm Spine Center.
Contact person: Eva Kosek