Fibromyalgia Research
CHALLENGES AND OPPORTUNITIES
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 the causes or triggers of fibromyalgia.
Some scientists believe that the syndrome may be caused by 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.
Fibromyalgia patients 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 $70 million on pain research, which is conducted and supported
by 15 institutes, centers, and offices. However, 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 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
study 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 study will use genetics to screen for
single gene mutations that affect sleep patterns in the mouse.
Understanding this in the mouse 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.
In addition, NIAMS is currently funding research projects
related to understanding 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 stroke or burn injury patients who are having
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 experts from 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 all advances will come from, NIAMS strives to
support and maintain a diverse research portfolio. This is especially
important in the area of fibromyalgia, where many areas are
being developed simultaneously. Advancing understanding about
fibromyalgia requires both basic and clinical research projects.
Because basic research appears so far removed from actual patients
suffering from 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. For example, 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 what the molecules are that link sleep
and consolidation of long-term memory. Understanding this relationship
in 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 arthritic and musculoskeletal conditions. Behavioral
and social factors are important 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; 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 some 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
two mechanisms: investigator-initiated research projects and
Multipurpose Arthritis and Musculoskeletal Diseases Research
Centers. Applications for funding may be solicited by the Institute
(as with a request for applications [RFA]) or initiated by investigators.
In general, most of the research projects funded by NIH are
unsolicited research projects, known as investigator-initiated
grants. NIAMS has made awards in the area of fibromyalgia for
projects resulting both from solicited and unsolicited applications.
Applications submitted to NIH go through a two-step peer review
system. The design of this system is 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 may make 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 of the approach, the 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.
Recent 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 lifespan 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
investigator-initiated research projects and exploratory/developmental
projects that will 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 have joined NIAMS in issuing this RFA.
These include the National Institute of Dental Research (NIDR),
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 Office of Alternative Medicine, the Office of Research on
Women's Health, and the Office of Behavioral and Social Sciences
Research.
Acupuncture Clinical Trials-Program Announcement. In
February 1998, the NIH Office of 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 21 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 a request for applications issued
by the National Heart, Lung, and Blood Institute, NIAMS, and
several other NIH institutes. The NIAMS grants are basic research
studies and will focus on rest and long-term memory consolidation
in drosophila and on the genetics of sleep and rest behavior
in the mouse.
Scientific Workshop: The Neuroscience and Endocrinology
of Fibromyalgia. In July 1996, NIAMS sponsored a scientific
workshop that explored recent 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 presentations and discussion was
recently 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 mentioned previously.
Fibromyalgia Advocate Appointed to Institute Advisory Council.
A leading advocate for fibromyalgia, Ms. Tamara Liller, President
of the Fibromyalgia Association of Greater Washington, Inc.,
recently joined 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.
E-text updated: October 1998
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