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.