Fibromyalgia
Research: Challenges and Opportunities
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.
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.
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.
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.
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), a part of the National Institutes of Health (NIH), 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. The National
Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is
a public service sponsored by the NIAMS that provides health information and information
sources. Additional information can be found on the NIAMS Web site at http://www.niams.nih.gov/.
Reprinted with the permission of:
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIAMS/National Institutes of Health
1 AMS Circle
Bethesda, MD 20892-3675
Publication Date December, 1999
The National Arthritis and
Musculoskeletal and Skin Diseases Information Clearinghouse (NAMSIC) is a public service
sponsored by the NIAMS that provides health information and information sources. The
NIAMS, a part of the National Institutes of Health (NIH), leads the Federal medical
research effort in arthritis and musculoskeletal and skin diseases. The NIAMS sponsors
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