Our research- Molecular pain
Chronic pain is a major health problem affecting about 20 per cent of the Swedish population, resulting in markedly reduced quality of life for the individual.
Nearly 1 in 5 adults suffer from chronic pain. Drug development has hitherto been insufficient and there are currently few effective treatments for persistent pain. Without adequate relief, individuals with persistent pain often endure physical and psychosocial problems resulting in a dramatically reduced quality of life. Pain is not only devastating for the individual but also imparts large societal and economic costs in the form of medical care, sick leave and lost productivity. Thus, it is critical to increase our understanding of how chronic pain is regulated, in order to identify new treatment strategies and novel drug targets for pain relief.
Pain is one of the most problematic symptoms of rheumatic diseases, such as rheumatoid arthritis (RA) osteoarthritis (OA) and fibromyalgia (FM). RA is an autoimmune disease characterized by joint inflammation along with bone and cartilage destruction that affects around 1% of the population. In RA, current anti-inflammatory treatments effectively control joint-inflammation (and inflammatory pain) in many patients. Unfortunately, well-controlled joint inflammation does not mean pain relief. RA patients frequently present with debilitating pain prior to joint-inflammation, which often persists even when the disease is medically controlled or in remission. Effective analgesic therapies for the “non-inflammatory” pain are lacking. We identified that several RA-associated antibodies, isolated from RA patients, induce pain-like behavior without classical signs of inflammation when transferred to mice.
FM is a highly prevalent disease affecting 2-4% of the population, which predominantly affects women (7/10). Hallmarks of FM include widespread musculoskeletal pain, stiffness, and physical/cognitive fatigue. There is growing evidence of central nervous system (CNS) disturbances in FM, however, our lack of understanding the underlying pathophysiology has prevented development of effective therapies. Further, available treatments are often ineffective and frequently associated with adverse effects. FM is currently not considered an autoimmune disease, but we have discovered that transfer of antibodies (immunoglobulin G, IgG) purified from FM patients’ blood to mice gives rise to an increased sensitivity to deep pressure and cold and a reduced activity without causing an overt tissue inflammation.
The insight that autoantibodies may generate pain in the absence of visible inflammation led us to the hypothesis that not only in RA, but also in FM, there are undiscovered links between antibodies and chronic pain. Several projects in the lab are centered on investigating mechanisms by which antibodies contribute to long-lasting pain, with a focus on the molecular and cellular processes responsible for pronociceptive properties of antibodies, and the consequences of their actions.