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Fibromyalgia
Research
Fibromyalgia Research: Challenges &
Opportunities
From NIAMS
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.
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