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Highlights
August 2004
Spotlight on Research
By Year
Fibromyalgia: Summaries of Research
We created this document because we frequently receive requests from the public about the status of the studies listed in the 1999 press release, “NIAMS Funds Multiple Research Grants in Fibromyalgia,” as well as on other more recent studies.
A Controlled Family Study in Patients with Fibromyalgia
Principal investigator: Lesley M. Arnold, M.D.
Goal of study: To compare the prevalence of fibromyalgia and mood disorders among the family members of people with fibromyalgia with the prevalence of those disorders among the family members of people with rheumatoid arthritis.
Description: Recent studies with small numbers of participants suggest that fibromyalgia runs in families. Previous studies also suggest that people with fibromyalgia are more likely to have relatives with major mood disorders (such as major depression and bipolar disorder) than other people with chronic pain conditions, such as rheumatoid arthritis.
To explore and further test those results with a large group of participants, Dr. Arnold and her colleagues interviewed 78 people with fibromyalgia and collected information about more than 500 of their relatives to determine the prevalence of fibromyalgia and mood disorders in the family members. For comparison, her team also interviewed 40 people with rheumatoid arthritis and collected information about 272 of their relatives.
The researchers needed to study people with rheumatoid arthritis to create a control group, which reduces the possibility of bias in a study. Collecting the same information from the rheumatoid arthritis group that they take from the fibromyalgia group allows the researchers to compare the fibromyalgia data with that of people who do not have fibromyalgia but are similar to them in terms of background characteristics and treatment-seeking behavior.
Progress and conclusions: The researchers found that fibromyalgia aggregates in families, which means that the family members of people with fibromyalgia were much more likely to have fibromyalgia than family members of people with rheumatoid arthritis.
The team also found that fibromyalgia coaggregates with major mood disorders in families, which means that the family members of those with fibromyalgia were much more likely to have a major mood disorder than the family members of those who have rheumatoid arthritis.
The researchers say one implication of these findings is that genetic factors may play a role in fibromyalgia. In addition, they speculate that mood disorders and fibromyalgia may share some inherited factors.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Outcomes in Young Women with Fibromyalgia
Principal investigator: Carol S. Burckhardt, Ph.D.
Goal of study: To develop a model to plan early intervention strategies that minimize fibromyalgia-related disabilities and maximize health status in young women with the syndrome.
Description: The project focused on describing how fibromyalgia affects the lives of young women during the first year after diagnosis. The investigators recruited 98 women (48 in the United States, 50 from Sweden) between the ages of 18 and 39. Participants were interviewed within 6 months of diagnosis and again 6 months and 12 months later. They were asked questions about their employment, medications, diet, health provider visits, other illnesses, social support, strategies for dealing with symptoms, and their physical, psychological, and social difficulties. They were also asked their marital status, how many children they had, and their education level. The women answered self-report questionnaires that measured depression, anxiety, pain-coping strategies, and self-efficacy. (A person’s self-efficacy is the degree to which he or she believes one can controls the effects of one’s health problem.)
Progress and conclusions: Participants in both countries agreed that difficulties maintaining personal, work, and social roles arose from sources such as pain, severe fatigue, high stress, an inability to concentrate, standing or sitting for long periods of time, heavy lifting, and a lack of understanding by employers, colleagues, and family members. At the time of diagnosis, 71 percent of women interviewed were employed. By the time of the first study interview, that percentage had dropped to 60 percent. Twelve months after that first interview, 41 percent were employed. Predictors of unemployment included age (younger people were more likely to be unemployed), low physical functioning, pain severity that interferes with the ability to work, and a lack of belief in one’s ability to control pain.
Preliminary findings suggest that early intervention to assist newly diagnosed young women might lead to better outcomes in health status and quality of life. Useful interventions would be those that help women maintain paid employment, learn ways to manage their pain and fatigue, engage in physical exercise, maintain leisure activity, and encourage support from their social system.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Neuroendocrine Alterations in Fibromyalgia and Irritable Bowel Syndrome
Principal investigator: Lin Chang, M.D.
Goal of study: To identify central mechanisms within the brain that are involved in the body’s sensitivity to muscular and abdominal pain in fibromyalgia and irritable bowel syndrome.
Description: Irritable bowel syndrome (IBS) is a condition characterized by chronic or recurrent abdominal pain. Fibromyalgia is characterized by widespread muscle pain. Despite the difference in the location of body pain in these two syndromes, similarities in the conditions have led researchers to suspect there may be a similar central nervous system problem in both. Similarities of the syndromes include that both are common, both affect mainly women, and both often occur together.
To research their hypothesis about a central nervous system problem in IBS and fibromyalgia, Dr. Chang and her colleagues compared activation in the brain areas associated with pain processing in people who had IBS with people who had fibromyalgia. They measured brain activity in response to rectal inflation, which is an abdominal stressor, and to muscle pressure. Brain activation was measured by positron emission tomography (PET), an imaging technique that can measure blood flow to the brain.
Progress and conclusions: The researchers found that women with IBS demonstrated more activity in an area of the brain called the anterior midcingulate cortex when they experienced the rectal pressure than when muscle pressure was applied to their arms. The midcingulate cortex is a pain-processing area of the brain that commonly is activated in studies of muscular and abdominal pain.
In women with both IBS and fibromyalgia, the same brain area was more activated following muscle pressure than following rectal pressure. The researchers say these findings suggest that although the site of body pain is different in IBS and fibromyalgia, the central nervous system mechanisms underlying pain are probably similar. A better understanding of these mechanisms may lead to the development of more effective treatments for these conditions in the future.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Chronic Low Back Pain as a Model of Fibromyalgia
Principal investigator: Daniel J. Clauw, M.D.
Goal of study: To compare mechanisms of pain and tenderness in patients with two chronic pain conditions: chronic low back pain and fibromyalgia.
Description: For many people with chronic low back pain, as for people with fibromyalgia, there is no identifiable, physiologic cause of pain. Researchers have used sensory testing and magnetic resonance imaging (MRI) of the brain to identify generalized pain sensitivity and altered brain processing in people with fibromyalgia. These findings suggest that the central nervous system is somehow augmenting pain. Researchers suspect this also may be the case for a subset of people with low back pain. In other words, their back pain has more to do with the way their bodies process pain signals than with their backs.
To test this theory, Dr. Clauw and his research team used MRI and pain testing to study three groups of people:
- one with chronic low back pain that is not explained by MRI or x-ray findings,
- one with fibromyalgia, and
- one without either low back pain or fibromyalgia.
They conducted pain tests with a computerized device that applies pressure to the thumbnail. Participants from the three groups rated their pain at various levels of pressure. The researchers then used MRI to measure activity in areas of the brain that process pain. Using MRI provides objective evidence of the pain that study participants report.
Progress and conclusions: At equal pressures, those in the chronic low back pain group and those in the fibromyalgia group reported significantly more pain than people without either condition. Also, the MRI data showed more extensive activity in the areas of the brain that process pain in both these groups. These findings supported previous studies that found people with fibromyalgia report a high amount of pain – and show brain activity that corresponds with their reports – when a low amount or pressure is applied.
The novel finding of Dr. Clauw’s team, however, is that people with low back pain experienced just as much tenderness and sensitivity in response to thumbnail pressure as did the people with fibromyalgia. They also showed the same types of brain activation. These results suggest that understanding chronic low back pain better may lead to more effective treatments for it and could discourage the use of surgery and medications that will not help for this particular subset of people with back pain.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Behavioral Insomnia Therapy for Fibromyalgia Patients
Principal investigator: Jack Edinger, Ph.D.
Goal of study: To evaluate the effectiveness of cognitive-behavioral therapy for insomnia in fibromyalgia patients.
Description: Sleep disorders, including insomnia, are common in people with fibromyalgia. To determine whether cognitive behavioral therapies might improve insomnia in fibromyalgia patients, investigators enrolled 47 people with fibromyalgia in the study. Cognitive behavioral therapies in this study mean therapies designed to educate people about sleep and to correct bad sleep habits and improper sleep scheduling. Participants were randomized into groups, each employing one of the following therapies:
- cognitive behavioral therapy,
- usual care (typically medications) from the doctor treating their fibromyalgia,
- sleep hygiene, which includes, for example, instructions to limit caffeine, increase exercise, avoid alcohol close to bedtime, and keep the bedroom dark and quiet.
All participants also kept sleep logs and answered questionnaires before and after treatment about their insomnia symptoms, their beliefs and attitudes about sleep, and the extent to which they felt they could control their sleep problems.
Progress and conclusions: To date, the researchers have analyzed data from the first 41 study participants, and they show trends suggesting that cognitive behavioral therapy is more effective than the other treatments. For example, the researchers’ analysis of the sleep log data showed that people in the cognitive behavioral therapy group experienced more improvement in how long they slept than the other two groups. The analysis of the questionnaire data showed that those in both the cognitive behavioral therapy group and the sleep hygiene group had significantly greater improvements in their subjective insomnia symptoms than did the group receiving usual care.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Noradrenergic Dysfunction: A Model of Fibromyalgia Pain
Principal investigator: Luc Jasmin, M.D., Ph.D.
Goal of study: To examine the role of noradrenaline (norepinephrine) in chronic pain by studying mice lacking this neurotransmitter throughout their bodies and rats lacking it in their brains and spinal cords.
Description: Noradrenaline, a substance in the body that functions as both a stress hormone and a neurotransmitter (a chemical messenger), is important for many body functions, including the regulation of pain. Some researchers hypothesize that fibromyalgia is somehow linked to a lack of noradrenaline, yet medications that act on noradrenaline have only been a limited success for treating chronic pain syndromes.
To better understand the role of noradrenaline in chronic pain, Dr. Jasmin and a team of researchers studied pain response in rodents that lacked the hormone and neurotransmitter. The team used mice that had been genetically altered to lack noradrenaline before birth. The team also used adult rats, giving them a drug that wipes out the noradrenaline-producing cells in the central nervous system.
Progress and conclusions: Both the mice and the rats had lower pain thresholds than animals with normal noradrenaline levels. The effect of treatment on pain thresholds was less pronounced for the rats than the mice. This result may be due to the fact that the rats’ noradrenaline levels were depleted later in life, as adults – a scenario that more closely mimics what might occur in humans than the mouse model. (Human beings are rarely born without noradrenaline. It is necessary for fetal development.)
In rats, as in people with fibromyalgia, drugs designed to act on noradrenaline had little effect on pain, suggesting that although a noradrenaline deficit probably plays a role in chronic pain, other chemical anomalies in pain circuits also may play a critical role in the condition.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and co-funded by the NIH’s Office of Research on Women’s Health.
Neurotrophins and an Animal Model of Fibromyalgia
Principal Investigator: Alice A. Larson, Ph.D.
Goal of study: To better understand the processes involved in stimulating and regulating pain in rodents as a model for humans.
Description: The primary role of amino acids is to serve as building blocks for proteins in the body, but Dr. Larson and her colleagues have found that at least two of them, glutamate and aspartate, have another important function: helping to transmit pain information to the brain.
To understand better the function of these two amino acid neurotransmitters, as well as the role of other neurotransmitters in painful conditions such as fibromyalgia, the researchers attempted to create an animal model of chronic pain in rats. They did so by injecting rats with kainic acid, a compound derived from seaweed that mimics the effects of the two amino acids.
Progress and conclusions: A single injection of kainic acid to the vagus nerve – one of the nerves in the brain that supplies nerve fibers to the organs of the chest and the abdomen – was found to enhance long-term pain sensitivity in a fashion that is relatively insensitive to high doses of morphine. As such, rodents receiving the injection are proving useful for the study of chronic pain mechanisms.
The scientists can’t say how closely the syndrome they have created mimics fibromyalgia, but comparing what is happening in their model to what is happening in fibromyalgia should give them important information about both. The eventual goal is to use the model not only to better understand chronic pain, but also to develop new treatments for it.
This study was funded by the National Institute of Neurological Disorders and Stroke and co-funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Autonomic Stress-Reactivity in Fibromyalgia
Principal investigator: Akiko Okifuji, Ph.D.
Goal of study: To employ a novel method to assess the association between pain sensitivity in fibromyalgia and the autonomic nervous system’s reaction to stress.
Description: Although the cause of fibromyalgia is not well understood, the accumulation of research seems to indicate that the syndrome is associated with problems in the way the body responds to stress. In particular, past studies suggest that the nervous systems of people with fibromyalgia react less vigorously than others to physical, emotional, and environmental stressors. (Environmental stressors include noise, light, or temperature changes).
In Dr. Okifuji’s study, researchers are investigating the relationship between fibromyalgia pain and the autonomic nervous system, which is the part of the nervous system that directs body functions that are not consciously controlled, such as the heartbeat and intestinal movements. The study involves two groups of women, one with fibromyalgia and one without. Each group is given a widely used test, called the postural challenge stressor, which involves having the women rise quickly from a lying position. Blood pressure measurements taken after the women rise allow the researchers to assess and compare the ability of the women’s autonomic nervous systems to adjust to physiologic stress.
Progress and conclusions: The study has involved 90 women (21 with fibromyalgia and 69 without) to date. Preliminary results show that the women with fibromyalgia did not react abnormally to the postural stressor. In general, the researchers think there appears to be a modest relationship between the women’s sensitivity to the tender points associated with fibromyalgia and their blood pressure reaction to the postural stressor. A complete analysis of the data is underway.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Mapping Genes for Fibromyalgia
Principal Investigator: Jane Olson, Ph.D.
Goal of study: To identify genes that predispose to fibromyalgia in order to better understand the causes and biological mechanisms of this illness.
Description: Because fibromyalgia often occurs in more than one member of a family, researchers suspect that there may be a genetic component to the syndrome. Dr. Olson’s team is identifying and collecting medical information from participant families in which two or more members have fibromyalgia. The data collected comes from routine blood tests, physical examinations (including tender point examinations), medical histories, genetic measurements of DNA and measurements of platelet serotonin. (Serotonin is a chemical found primarily in the blood platelets, as well as in the intestinal wall and the central nervous system. It is believed to play a role in inflammation and also acts as a neurotransmitter (a nervous system signaling molecule), especially in the sleep process.) Family members also are asked to fill out questionnaires relating to their physical activity and health status.
Progress and conclusions: To date, more than 140 families have participated in the study, and researchers have begun the genetic analyses. They think initial results confirm that the genes associated with serotonin play a role in fibromyalgia. The researchers expect to make more comprehensive results available next year.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Fibromyalgia and TMD in Young Women – a Multiracial Study
Principal investigator: Octavia Plesh, M.D.
Goal of study: To study risk factors associated with temporomandibular disorder (TMD) in fibromyalgia in young women participating in the National Heart, Lung, and Blood Institute Growth and Health Study.
Description: Clinical observations and reports show that the majority of people who see doctors for the widespread pain of fibromyalgia also have localized pain around the jaw and face region, a condition known as temporomandibular disorder (TMD).
Using questionnaires and clinical examinations, the researchers studied the prevalence (the total number of cases) and the incidence (the number of new cases over a given period of time) of fibromyalgia, regional chronic pain, and TMDs in a group of 1,500 women (half Caucasian, half African American) between the ages of 20 and 25. They also explored the potential relationships between these conditions.
Progress and conclusions: The team found that the more widespread a woman’s pain was, the more likely she was to have TMD. Interestingly, African Americans and Caucasians had similar patterns of pain, with the exception of temporomandibular pain, which occurred in about twice as many Caucasians as African Americans. The researchers are currently in the process of analyzing the data to determine other risk factors for TMD among young women with fibromyalgia.
This study was funded by the National Institute of Dental and Craniofacial Research and co-funded by the NIH’s Office of Research on Women’s Health.
Fibromyalgia, Depression, and Myofascial TMD
Principal Investigator: Karen G. Raphael, Ph.D.
Goal of study: To understand the reasons for the high rates of psychiatric disorders, especially depression, in women with fibromyalgia.
Description: Research in recent years suggests that women with fibromyalgia have high rates of mood disorders. To better understand the reason for the connection between mood disorders and fibromyalgia, Dr. Raphael’s team conducted a community-based study examining the rates of psychiatric disorders in family members of women with and without fibromyalgia. In a closely related study to better understand the role stress plays in fibromyalgia, the researchers interviewed 1,312 women in the New York metropolitan area about symptoms of fibromyalgia both before and after the Sept. 11, 2001, terrorist attacks on the World Trade Center.
Progress and conclusions: Preliminary findings indicate relatively high rates of depression among family members of women with fibromyalgia who themselves had no personal histories of depression. The researchers say this implies that rates of depression are high in women with fibromyalgia because the two conditions share risk factors that are probably related to a common genetic cause.
Other findings indicated that the trauma of the World Trade Center attacks was not associated with the worsening of fibromyalgia symptoms or the development of new fibromyalgia symptoms among women who did not have symptoms earlier. The research team did not find an association between the extent to which participants were exposed to the traumatic events of Sept. 11 and either the worsening of fibromyalgia symptoms or the development of new fibromyalgia symptoms.
The researchers think these findings suggest that fibromyalgia is probably not caused by stress, but instead that there is a link between depression and fibromyalgia that is commonly transmitted within the family, probably genetically.
This study was funded by the National Institute of Dental and Craniofacial Research.
Employment and Health Status in Women with Fibromyalgia
Principal Investigator: Susan T. Reisine, Ph.D.
Goal of study: To explore the relationship between paid work, family work, daily stress, and psychological health in women with fibromyalgia.
Description: For this study, researchers recruited 287 women with fibromyalgia (137 of whom were employed and 150 who were not) and 286 women without fibromyalgia who were matched to the other group in terms of age, race, and employment status. Each participant was asked to complete an annual telephone survey, with questions about health status, demographic characteristics, family structure, and workplace characteristics. They were also asked at the time of the interview to keep a daily diary in which they recorded stressful events, pain, and their mood for one week. They were also asked to complete an annual mail questionnaire that measures negative affectivity, a personality trait.
The research team then analyzed the results, focusing on the relationship between employment and measures of pain, fatigue, the number of painful areas of the body, and health status as assessed by the interview, questionnaire, and diary findings.
Progress and conclusions: The majority of participants – in particular those with demanding family work – reported high levels of symptoms and poor health status. However, analyses of the data showed that women who were employed reported significantly less pain, less fatigue, and a better ability to function than those who were not employed.
The researchers concluded that because of the negative effects of the demands of family work, the relationship between family demands and fibromyalgia severity is one that deserves greater attention by clinicians.
More research is needed to answer the question: Does being employed actually help a woman’s health status or does having better health simply enable women to stay in the workforce?
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Neurobiology of Chronic Muscle Pain
Principal Investigator: Kathleen Sluka, Ph.D.
Goal of study: To develop a new model of chronic, widespread pain and then use it to identify responsible mechanisms in the peripheral or central nervous systems.
Description: Though the onset of fibromyalgia is often linked to injury or trauma, researchers believe the pain is maintained by changes in the central nervous system as opposed to any ongoing tissue damage. To better understand how injury might trigger fibromyalgia pain and which central nervous system mechanisms might perpetuate it, Dr. Sluka and her colleagues attempted to create a fibromyalgia-like pain condition in laboratory mice and rats. To do so, the researchers injected the rodents’ calf muscles with an acidic saline solution. They then measured the rodents’ pain sensitivity using a test in which pressure is applied to the rodents’ paws, much as doctors apply pressure to potential tender points on people’s bodies to diagnose fibromyalgia.
The team found that two injections, given 2 days to 5 days apart, produced a long-lasting, hypersensitivity that affected pain on both sides of the mice and rats’ bodies, and that certain drugs (such as morphine or compounds injected directly into the spinal cord to block a protein called N-methyl-D-aspartate, or NMDA) reversed the problem.
Progress and conclusions: Now that they have created and confirmed a mouse and rat model of chronic pain, the researchers are using the model to test potential pain mechanisms, including the role of NMDA receptors and other proteins believed to play a role in pain-processing in the spinal cord. The researchers also are investigating the possibility that changes occur in the genes of people with chronic pain conditions that lead to the production of more pain-producing proteins. The researchers’ eventual goal is to find ways to block the production or actions of these proteins.
This study was funded by the National Institute of Neurological Disorders and Stroke and co-funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
N-of-1 Trials to Assess FMS Therapies
Principal Investigator: Deborah Zucker, Ph.D., M.D.
Goal of study: To compare the effectiveness of antidepressant combinations for fibromyalgia in community practice settings using a new method that involves the combination of individual patient studies.
Description: Although many medications are potentially useful for treating fibromyalgia, finding the most effective medication or combination of medications for individuals can be a challenge. Often, in practice, this process is one of trial and error, involving prescribing and then assessing the effectiveness of new, potentially beneficial therapies for the individual. If this process could be carried out in a scientifically rigorous manner, Dr. Zucker and her colleagues reasoned, the collective information could contribute to the understanding of patients’ response to medical treatments.
As a part of their study, the researchers developed a method to test drug effectiveness using scientifically rigorous individual trials (referred to as n-of-1 trials because the number of participants is 1). They then used the method to test the effectiveness of the antidepressant combination amitriptyline and fluoxetine with that of amitriptyline alone.
The 58 study participants underwent six 6-week medication cycles in which they took the single antidepressant for a total of three periods and the antidepressant combination for a total of three periods. The participants did not know at any point which treatment they were receiving. Their symptoms were assessed during each period.
Progress and conclusions: At the completion of each study, participants received their analyzed results and together with their physician made their treatment decisions. The researchers also followed up 3 months later to assess their symptoms and medications again.
The researchers are now in the process of analyzing results from all the participants to determine the overall treatment results and to compare these findings with published results of standard clinical trials. The researchers also have explored attitudes about the feasibility of expanding this research approach among a broader group.
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and co-funded by the NIH’s Office of Research on Women’s Health.
