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Patient             Research RegistriesOutreach             ProgramsNIAMS             Coalition Members | Health TopicsPublication Date December 1999
Fibromyalgia Research: Challenges and Opportunities
- Background           on Fibromyalgia
- Research           on Fibromyalgia
- Why           Is Basic Research Important to Understanding Fibromyalgia?
- Why           Is Behavioral Research Important to Understanding Fibromyalgia?
- How           Are Fibromyalgia Grants Selected for Funding by NIAMS?
- Research           Initiatives

Background         on Fibromyalgia

Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal         pain, fatigue, and tenderness in localized areas of the neck, spine, shoulders,         and hips called "tender points." People with this syndrome may also experience         sleep disturbances, morning stiffness, irritable bowel syndrome, anxiety,         and other symptoms. Available data suggest that the number of persons         aged 18 and older in the United States with fibromyalgia is approximately         3.7 million. It primarily occurs in women of childbearing age, but children,         the elderly, and men may also be affected. 

Although the cause of fibromyalgia is unknown, researchers have several         theories about what triggers the disease. Some scientists believe that         the syndrome may result from an injury or trauma. This injury may affect         the central nervous system. Fibromyalgia may be associated with changes         in muscle metabolism, such as decreased blood flow, causing fatigue and         decreased strength. Others believe the syndrome may be triggered by an         infectious agent such as a virus in susceptible people, but no such agent         has been identified.       
Fibromyalgia is difficult to diagnose because many of the symptoms mimic         those of other diseases. The American College of Rheumatology (ACR) has         developed criteria for fibromyalgia that physicians can use in diagnosing         the disease. According to ACR criteria, a person is considered to have         fibromyalgia if he or she has widespread pain for at least 3 months in         combination with tenderness in at least 11 of 18 specific tender point         sites.       
Treatment of fibromyalgia requires a comprehensive approach. The physician,         physical therapist, and others in the medical support system, as well         as the patient, may all play an active role in the management of fibromyalgia.         Studies have shown that aerobic exercise, such as swimming and walking,         improves muscle fitness and reduces muscle pain and tenderness. Heat and         massage may also give short-term relief. Antidepressant medications may         help elevate mood, improve quality of sleep, and relax muscles. People         with fibromyalgia may benefit from a combination of exercise, medication,         physical therapy, and relaxation.      
Research         on Fibromyalgia       
Support of fundamental research is extremely important in fibromyalgia         as well as in many disorders characterized by pain and sleep abnormalities,         and many disciplines of medical research contribute to the knowledge base         in understanding these symptoms. Since it is impossible to know with certainty         which area will produce the next important discovery, the community of         science, of which the National Institute of Arthritis and Musculoskeletal         and Skin Diseases (NIAMS) is a part, has to be open to all ideas. Discoveries         can come from research funded in a variety of areas. For example, the         National Institutes of Health (NIH) supports pain research at different         levels--from the gene, molecule, cell, and organ to the human organism         itself. NIH spends more than $75 million on pain research, which is conducted         and supported by 15 institutes, centers, and offices. While this figure         would not be reported as funding for fibromyalgia research specifically,         certain aspects of pain research are applicable to understanding      fibromyalgia.       
The research on fibromyalgia supported by NIAMS covers a broad spectrum         from basic research to clinical studies to behavioral interventions. For         example, NIAMS investigators are examining the interactions between the         nervous system and the endocrine (hormonal) system and regulation of adrenal         function in fibromyalgia patients. Studies have shown that abnormally         low levels of the hormone cortisol may be associated with fibromyalgia.         Researchers are studying regulation of the function of the adrenal glands         (which make cortisol) in fibromyalgia. People whose bodies make inadequate         amounts of cortisol experience many of the same symptoms as people with         fibromyalgia. It is hoped that these studies will increase understanding         about fibromyalgia and may suggest new ways to treat the disorder.       
Basic research studies to advance our understanding of the molecular         and genetic basis of sleep and sleep disorders are also included in the         NIAMS research portfolio. One specific project on mice focuses on identifying         genetic factors that underlie molecular events involved in the regulation         of sleep. A wealth of information on the neuroanatomy, neurochemistry,         and neurophysiology of sleep provides a firm foundation for a genetic         approach to studies of sleep. This project will use genetics to screen         for single gene mutations that affect sleep patterns in mice. Understanding         this in mice will advance understanding of how this translates to humans.         Other basic research studies using animal models are investigating the         link between sleep and long-term memory.       
Examples of NIAMS-supported clinical research in fibromyalgia include         comparing pain mechanisms in this disorder and low back pain; determining         if aerobic exercise benefits patients with fibromyalgia through the action         of the hypothalamus and pituitary and adrenal glands; and studying neuroendocrine         changes in fibromyalgia and irritable bowel syndrome. The Institute is         also funding a new clinical trial to determine the effectiveness of combining         two antidepressants in treating the disorder.       
In addition, NIAMS is currently funding research projects related to         the role of behavioral factors in fibromyalgia. Investigators are evaluating         the effects of two of the most promising nonpharmacologic interventions         for fibromyalgia: cognitive behavioral therapy for pain management and         physical exercise training. This study is designed to test the hypothesis         that combining cognitive behavioral therapy and physical training will         be more effective than cognitive behavioral therapy or exercise alone.         If the cognitive and exercise interventions have synergistic effects in         fibromyalgia patients, future studies could evaluate this combination         in patients with other rheumatic diseases, or in those with stroke or         burn injuries who are experiencing pain during exercise/rehabilitation         regimens.       
Providing social support and education about one's disease or disorder         has been shown to be an effective means for improving the health care         status of individuals with chronic diseases. Studies are currently underway         focusing on patients with fibromyalgia to advance understanding of how         social support and education interventions may be helpful to these patients         as well.       
Why         Is Basic Research Important to Understanding Fibromyalgia?       
The research mission of NIAMS is broad and diverse. Progress in one area         of the Institute provides important clues for research in other areas.         Similarly, progress in areas supported by other NIH institutes can and         does provide valuable information for diseases within the NIAMS research         portfolio. That is why it is essential to support studies across the research         spectrum and to encourage cross-fertilization of knowledge from experts         in many disciplines. Studies on the neuroendocrine system, pain and sleep         disorders, and rheumatic and autoimmune diseases all may lead to a better         understanding of fibromyalgia.       
Since not all the outcomes can be anticipated, and it is hard to know         where scientific advances will come from, NIAMS strives to support and         maintain a diverse research portfolio. This is especially important in         fibromyalgia, where many areas are being developed simultaneously. Advances         against fibromyalgia require both basic and clinical research projects.         Because basic research appears so far removed from actual patients coping         with the disease, the benefits derived from this type of research may         not be so obvious.       
For many diseases and conditions, including fibromyalgia, basic research         must be done in order to obtain fundamental clues that direct research         in humans. Basic research is usually done in systems that are simpler         than the human system, so that the experimental variables can be manipulated         to observe changes in structure and function. This provides a general         understanding of biological events that may affect humans. Simpler organisms         used include bacteria, yeast, fruit flies (Drosophila), and mice. For         example, researchers study the fruit fly because it is more complex than         a bacterium, but can easily be maintained in a laboratory. In addition,         fruit flies have been studied for many years, and a great deal is known         about their genetics, biochemistry, and behavior. Scientists recently         discovered that mutations in the human version of a gene that controls         fruit fly growth and development are the likely cause of both the basal         cell nevus syndrome, a rare inherited disorder, and sporadic basal cell         carcinoma of the skin, the most common human cancer. In terms of fibromyalgia         research, studies in fruit flies may tell us which molecules link sleep         and consolidation of long-term memory. Understanding this relationship         in fruit flies may provide clues and research tools that will enable investigators         to learn why people with chronic sleep disturbances experience problems         with memory.       
Why         Is Behavioral Research Important to Understanding Fibromyalgia?       
Behavioral and social sciences research is an important area of investigation         at NIH and cuts across a wide range of research topics. NIAMS has long         supported behavioral research related to many rheumatic and musculoskeletal         conditions. Behavioral and social factors are significant contributors         to health and illness, frequently interact with biological factors to         influence health outcomes, and represent critical avenues for treatment         and prevention.       
Behavioral and social sciences research encompasses a wide array of disciplines.         The field employs a variety of methodological approaches including surveys         and questionnaires, interviews, randomized clinical trials, direct observation,         physiological manipulation and recording, descriptive methods, laboratory         and field experiments, standardized tests, economic analyses, statistical         modeling, ethnography, and evaluation. In addition, several key crosscutting         themes are characteristic of social and behavioral sciences research.         These include an emphasis on theory-driven research; the search for general         principles of behavioral and social functioning; the importance ascribed         to a developmental, life-span perspective; an emphasis on individual variation         and variation across sociodemographic categories such as gender, age,         and sociocultural status; and a focus on both the social and biological         context of behavior.       
Behavioral and social sciences research is important to understanding         how to better treat some of the clinically challenging symptoms that are         experienced by fibromyalgia patients. Research opportunities include behavioral         research on all aspects of fibromyalgia, including the relationships among         disturbed sleep, inactivity, pain, and depression that are often observed         in patients with fibromyalgia, and the development of innovative approaches         for treatment.      
How         Are Fibromyalgia Grants Selected for Funding by NIAMS?       
NIAMS currently supports research on fibromyalgia through investigator-initiated         research projects, Institute-solicited studies (funded in response to         a request for applications [RFA]), and Multipurpose Arthritis and Musculoskeletal         Diseases Research Centers. In general, most of the research projects funded         by NIH are unsolicited investigator-initiated grants. NIAMS has made awards         in the area of fibromyalgia for projects resulting from both solicited         and unsolicited applications.       
Applications submitted to NIH go through a two-step peer review system.         The design of this system is such that applications from researchers are         reviewed first by study sections for their scientific merit. Applications         for research on fibromyalgia may be reviewed by the Chronic Fatigue Syndrome         Special Emphasis Panel or by other relevant panels, depending on the expertise         required. The second level of review is each Institute's advisory council,         which assesses the relevance and priority of proposed projects, and makes         recommendations on funding particular meritorious applications.       
Primary consideration for funding is scientific merit. This is determined         during the review process and is reflective of the soundness and innovativeness         of the approach, the qualifications of the investigators, the potential         significance of the work, and the overall research environment. This process         is used throughout NIH for applications in all diseases and areas of science.         The reviewers are asked to evaluate the significance of the research proposal         in terms of improving understanding of an area of research or disease,         advancing scientific knowledge, learning about the mechanisms that cause         symptoms and signs of disease, or developing new treatments or prevention         strategies.       
Research         Initiatives       
**New Directions in Pain Research--Program Announcement.**         In September 1998, NIAMS joined 10 other NIH components in issuing a program         announcement (PA) entitled "New Directions in Pain Research." The purpose         of the PA is to inform the scientific community of broad, shared interests         in pain research across the various components of the NIH, and to stimulate         and encourage a wide range of basic, translational, and patient-oriented         clinical studies on pain. Applications are encouraged to study pain throughout         the life span from the perspectives of molecular genetics; transcriptional         controls; signal transduction, including cellular/molecular mechanisms;         innovative imaging technologies; plasticity; and hormonal or gender influences.         The goal of the PA is to advance the development of novel pain interventions,         treatments, and management strategies.       
**Basic and Clinical Research on Fibromyalgia--Request         for Applications.** In March 1998, NIAMS issued an RFA to promote         research studies and exploratory/developmental projects to advance understanding         of fibromyalgia and related disorders and provide critical new knowledge         needed for the treatment and prevention of the syndrome. Several NIH institutes         and offices joined NIAMS in issuing this RFA. These include the National         Institute of Dental and Craniofacial Research (NIDCR), which has an interest         in pain and the relationship between temporomandibular disorders and fibromyalgia;         the National Institute of Neurological Disorders and Stroke (NINDS), which         has an interest in pain research; and three offices within the NIH Office         of the Director: the National Center for Complementary and Alternative         Medicine, the Office of Research on Women's Health, and the Office of         Behavioral and Social Sciences Research.       
In addition to the announcement being listed in the usual manner on the         World Wide Web in the NIH         Guide to Grants and Contracts, NIAMS distributed over 1,600 copies         of the announcement to individual investigators and organizations to stimulate         an interest in fibromyalgia research. NIAMS grantees in fibromyalgia,         arthritis, and muscle diseases, as well as in the Centers program, received         copies, as did grantees NIH-wide in the fields of chronic pain, chronic         fatigue syndrome, sleep, neuroendocrinology, and other related fields.       
As a result of the RFA, NIAMS and its sister institutes and offices funded         15 new fibromyalgia projects--totaling more than $3.6 million--in 1999.       
**Acupuncture Clinical Trials--Program Announcement.**      In February 1998, the NIH Office of Alternative Medicine (now the         National Center for Complementary and Alternative Medicine), along with         six NIH institutes, including NIAMS and NINDS, and the Agency for Health         Care Policy and Research, issued a PA entitled "Acupuncture Clinical Trial         Pilot Grants." The objective of the PA is to increase the quality of clinical         research evaluating the efficacy of acupuncture for the treatment or prevention         of disease and accompanying symptoms. Back pain, cancer, fibromyalgia,         temporomandibular disorders, HIV/AIDS, and reflex sympathetic dystrophy         are among the diseases and conditions identified in the PA.       
**NIH Pain Research Consortium--Conferences.**         The NIH-wide Pain Research Consortium encourages information sharing and         collaborative research efforts, provides coordination of pain research         across all NIH components, and ensures that results of NIH-sponsored pain         research are widely communicated. A major goal of the Consortium is to         coordinate efforts across the many NIH components to develop a better         understanding of what causes pain, so better treatments are available         to people with painful disorders such as fibromyalgia. The Consortium         sponsored a symposium entitled "New Directions in Pain Research" on November         20-21, 1997, and a second conference entitled "Gender and Pain" on April         7-8, 1998.       
**Molecular Biology and Genetics of Sleep and         Sleep Disorders--Request for Applications**. In fiscal year 1997,         NIAMS awarded two grants submitted in response to an RFA issued by the         National Heart, Lung, and Blood Institute, NIAMS, and several other NIH         institutes. The NIAMS grants are basic research studies and focus on rest         and long-term memory consolidation in fruit flies and on the genetics         of sleep and rest behavior in mice.       
**The Neuroscience and Endocrinology of Fibromyalgia:         A Scientific Workshop**. In July 1996, NIAMS and several other         NIH organizations sponsored a scientific workshop that explored advances         in the neuroscience and endocrinology of fibromyalgia. The workshop focused         on chronic pain, neuroendocrinology, and sleep disorders associated with         fibromyalgia. What made this workshop so unusual and effective was its         design, which brought together researchers in the basic sciences of chronic         pain, neuroendocrinology, circadian rhythms, and sleep disorders--all         challenges for patients with fibromyalgia. These experts in basic research         were joined by clinicians who treat patients with fibromyalgia and by         a significant number of patients themselves. This multidisciplinary workshop         helped to identify research needs and opportunities, and the gaps in understanding         of this clinically challenging condition.       
The summary report of the workshop presentations and discussion was published         in *Arthritis and Rheumatism*, Vol. 40, No. 11, November 1997. Publication         of the summary of the workshop in this peer-reviewed journal provides         for wide distribution of the discussion of research opportunities to the         scientific community with interest in this disorder. The workshop also         led to the March 1998 RFA described previously.       
**Fibromyalgia Advocate on Institute Advisory         Council.** A leading advocate for fibromyalgia, Ms. Tamara Liller,         President of the Fibromyalgia Association of Greater Washington, Inc.,         is a member of the National Arthritis and Musculoskeletal and Skin Diseases         Advisory Council. The Advisory Council, which includes both scientific         and public members, meets three times a year and provides valuable input         to the Institute's priority-setting process.             
The mission             of the National Institute of Arthritis and Musculoskeletal and Skin             Diseases (NIAMS) is to support research into the causes, treatment,             and prevention of arthritis and musculoskeletal and skin diseases,             the training of basic and clinical scientists to carry out this research,             and the dissemination of information on research progress in these             diseases. For more information about NIAMS programs and topics, call             our information clearinghouse at (301) 495-4484.
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