UAB Researcher’s Focus Is Fibromyalgia’s Many Mysteries

UAB Researcher’s Focus Is Fibromyalgia’s Many Mysteries

Fibromyalgia syndrome (FMS) is a chronic illness of indeterminate cause, a syndrome — that is, a constellation of signs and symptoms observed in, and characteristic of, a single condition — and not a specific disease with clearly defined causes and treatments. It is typically characterized by moderate to severe musculoskeletal pain of at least three months’ duration that can’t be attributed to any definitive cause, and accompanied by fatigue, sleep disorders, restless legs syndrome, tension headaches, and other disorders.

There is a considerable degree of crossover between FMS symptom profiles and those associated with myalgic encephalomyelitis, or Chronic Fatigue Syndrome (CFS) — another poorly understood disorder of unknown etiology. The currently prevailing theory of causation is that fibromyalgia amplifies painful sensations by affecting how the brain processes pain signals.

The research goal of Dr. Jarred Younger’s Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama Birmingham is to end chronic pain and fatigue caused by inflammation in the brain for millions of people throughout the world through use of neuroimaging, pharmaceutical, and immunological techniques to better understand how inflammation affects people’s bodies and minds.

youngerJDr. Younger, who received his PhD in Experimental Psychophysiology in 2003 from the University of Tennessee, Knoxville, subsequently completed postdoctoral fellowships at Arizona State University and the Stanford University School of Medicine before taking an assistant professor position at Stanford. In 2014, he joined the faculty at the University of Alabama Birmingham, where he hopes to establish Alabama’s first research and clinical care center specializing in fibromyalgia and related conditions, including chronic fatigue syndrome and Gulf War illness.

As Director of the Neuroinflammation, Pain and Fatigue Lab, and a UAB Associate Professor, Dr. Younger’s primary appointment is in the UAB Department of Psychology, with secondary appointments in the Departments of Anesthesiology and Rheumatology. His work is currently funded by the National Institutes of Health, the Department of Defense, and several nonprofit agencies to develop techniques for diagnosing and treating neuroinflammation, pain, and fatigue.

The Younger lab research team have found specific chemicals in the blood that are part of the immune system and may not be working correctly, and consequently causing chronic pain and fatigue in many women. The lab has received funding from the National Institutes of Health to continue testing the role of these chemicals in disease, and say that if the researchers are successful, they may not only produce an objective test for fibromyalgia and chronic fatigue syndromes, but also be able to develop more effective treatments for those disorders.

Dr.Younger notes on the lab website that after the 1991 Gulf War, many individuals in the military returned home with a range of unexplained symptoms mostly involving chronic pain and/or fatigue. He believes that environmental exposures while in the Persian Gulf region may have sensitized the immune system, causing the so-called “Gulf War illness” symptoms, and the lab is testing that hypothesis by measuring several inflammatory chemicals in the blood of people who suffer from the condition with the objective to learn more about Gulf War illness and hopefully develop effective and safe treatments.

He observes that several botanical agents, such as mushrooms, nettles, and herbs, have anti-inflammatory properties that may benefit individuals with chronic pain or fatigue, and most of these products are available without a prescription, but have never been tested in Gulf War illness. The lab is currently funded by the Department of Defense to test some of these supplements in individuals with Gulf War illness, and if found to have anti-inflammatory qualities that reduce symptoms, the investigators will learn more about what is wrong in people with Gulf War illness and make progress in treatments that help them function and feel better.

Dr. Younger and his team believe that low-level inflammation in the brain may be the root of many cases of FMS/CFS pain, fatigue, problems with thinking or memory, and depression, but unfortunately there is no tool currently available that allows clinicians to determine whether someone has low-level brain inflammation. They are working on several solutions to this, such as using neuroimaging techniques like diffusion tensor imaging, positron emission tomography, and magnetic resonance spectroscopy, and hope to soon be able to make a safe, non-invasive and accurate test available for neuroinflammation. They are currently recruiting people with chronic pain and fatigue, and healthy people as controls to participate in these studies.

Regarding the use of painkiller drugs to treat fibromyalgia, Dr. Younger notes that while strong painkillers such as a range of opioid variants are important in managing pain, they may cause problems in some individuals when used for a long period of time, include addiction, changes in mood, and even increased sensitivity to pain. The lab team are conducting brain scans on people either starting or stopping opioid painkillers to determine how the drugs affect the brain. With the information they gain, they hope to find ways to improve pain treatments and minimize their unwanted side effects.

The lab has demonstrated that low doses of naltrexone, which belongs to a a class of medications called opiate antagonists that are primarily used along with counseling and social support to help people who have stopped drinking alcohol and using street drugs stay clean, can also be effective in reducing chronic pain associated with fibromyalgia. In a UAB Magazine feature story, Sarah C.P. Williams reports that in 2009 Dr. Younger first reported the effectiveness of low-dose naltrexone in women given 4.5 milligrams per day of the drug, reporting less pain throughout the weeks that they received it. The researchers believe the medication works for chronic pain by suppressing the activity of immune cells in the brain (microglia) that have become hypersensitized, and are currently further testing this medication along with other medications that they say may work even better than low-dose naltrexone.

Ms. Williams also cites Dr. Younger commenting on his hypothesis that Microglia, a type of glial cell that are the resident macrophages of the brain and spinal cord acting as the first and principal form of active immune defense in the central nervous system (CNS) and the brain “against everything,” are turned on in persons with both fibromyalgia and chronic fatigue when they’re not supposed to be, consequently causing fatigue or pain, a depressed mood, and cognitive dysfunction. Naltrexone is believed to stop activated microglia from producing inflammatory chemicals, and Ms. Williams says Dr. Younger is planning follow-up studies to find evidence supporting this idea, but faces a crucial challenge, since currently no methods are available to look directly at the activation or inflammation of microglia in living humans. However, he and his lab colleagues are working on solutions, including specialized brain scans that measure the temperature of the brain or the presence of certain chemicals.

Dr. Younger tells Ms. Williams that his discoveries have already begun to change the face of fibromyalgia and chronic fatigue research and treatment, but that his work is just beginning. He says it is essential to have a fuller understanding of what is wrong in order to find the best treatments for these disorders, noting that treatment of chronic fatigue syndrome and fibromyalgia is a decade or two behind other inflammatory diseases, such as rheumatoid arthritis, for which there are now effective treatments.

Sources:
University of Alabama Birmingham
UAB Neuroinflammation, Pain and Fatigue Laboratory
National Institutes of Health U.S. National Library of Medicine
UAB Magazine
lowdosenaltrexone.org
Wikipedia