What do you mean you’re sick and you need help? You look normal, and you seem to get around OK. Sure, you’re a little plump and out of shape, but so are many of my clients. I’ve got a time slot at 6:00am on Monday, Wednesday and Friday. See you bright and early tomorrow, and we’ll begin a fitness evaluation and the first step toward a new and better you. What? You don’t think you can make it tomorrow morning? You said you don’t work, and your kids are grown and on their own? You must by lazy. In a few days, you’ll get used to getting up early and feeling refreshed, ready to attack the day. You can’t make it before 10:00am because you’re in constant pain and have fibro… what? Fibromyalgia? What’s that? I never heard of that before. Is that a new disease? But you seem OK? Is it like arthritis or something?
Too often, this is a typical scenario trying to work with fibro clients who are anxious to begin an exercise program under your tutelage but reticent to begin without certain accommodations. Fibro clients are looking for PTs who are knowledgeable about their condition and willing to make the necessary adjustments that may involve spur-of-the-moment rescheduling, a nightmare to trainers.
In this article, we will lay out all that science can tell about fibromyalgia syndrome (FM). We will present a brief history of the disease followed by a discussion of the diagnosis and prevalence of FM in the US. Most of this article with focus upon suspected causes (although, to date, no one knows for sure). In a follow-up article by my wife, Colleen Black-Brown (click here to view), she will cover various treatment modalities including surgical, pharmacological and alternative approaches with special emphasis upon proper exercise progressions according to the phase or stage in which fibros find themselves. In both series, we will provide a significant list of references, although by no means complete. There are over 1,000 research studies reported in the literature. We will cull out the best of the best.
The story begins almost 200 years ago when a British surgeon, William Balfour, described a condition of pain and stiffness around muscle and overlying fibrous tissue, accompanied by fatigue. Twenty-five years later Valleix confirmed Balfour’s findings. Then in 1904, two authors (Gowers and Stockman) simultaneously reported a similar condition of inflamed nodules and soft-tissue syndrome producing tenderness and pain. One of the authors, Gowers, coined the term fibrositis, which stuck for over 75 years (and still does in some medical circles) and prescribed “perspiration” (i.e., exercise) instead of aspirin as the preferred treatment. Boy, was he ahead of his time. For many years, this condition was considered psychogenic because no blood or tissue tests could be performed that would adequately diagnose the condition, and there appeared to be extreme overlap with other diseases such as arthritis, lupus, chronic fatigue syndrome and rheumatica. In fact, it was not until 1987 that the American Medical Association recognized fibromyalgia syndrome (FM) as a major illness and a disabling condition.
After years of research, in 1990 a team of rheumatologists under the auspices of the American College of Rheumatology established and published definitive criteria for diagnosing FM. Prior to 1990, the diagnosis consisted mainly of excluding other diseases and finally assigning FM when no other disease could be adequately diagnosed. It is a difficult disease to diagnose. The key is to determine the location and sensitivity of “tender points” (Figures 3 and 4). Approximately 4 kg (10 pounds) of pressure is applied by the forefinger or thumb to each of nine pairs of tender points located bilaterally on both torsos and the trunk. A positive test consisted of pain felt in 11 of 18 tender points. If the person experienced pain (more than mere pressure), you can rate the pain on a scale of one to five. This is useful when your client is retested after a period of time to determine the effectiveness of your intervention program. One the authors was diagnosed six years ago with sero-negative rheumatoid arthritis. One year later, after a visit to Mayo Clinic, the diagnosis was changed to sero-negative lupus. Then four years ago, FM was determined to be the true cause of her discomfort and pain. As seen from Figure 1, the illness is characterized primarily by pain. It is not the type of pain that necessarily gets worse with time, nor does it result in death, but there are many characteristics associated with FM that are truly debilitating (Figure 2). The symptoms associated with FM can be classified into three categories:
Core, characteristic and common features.
- In the core category, it has been found that 100 percent of all FM patients experience generalized pain and widespread tenderness.
- More than 75 percent of FM patients possess characteristic features of chronic fatigue, disturbed sleep patterns and morning stiffness.
- Common features experienced by more than 25 percent of fibros include Raynaud’s phenomenon (tingling fingers), irritable bowel syndrome, headache, subjective feeling of swelling, paresthesia, various psychological abnormalities and some aspect of functional disability.
From a functional viewpoint, Mannerkorpi reported that FM patients demonstrate 30 to 50 percent reduction in aerobic capacity, reduced ROM and some reduction in muscle strength and endurance. This reduced physiological capacity requires an especially slow and delicate progression in the exercise program of fibros. White observed that fibros report more days in bed, more healthy years of life lost and greater disability versus control subjects. It also appears that pain and stiffness are more important as limiting factors in lifestyle habits of fibros than among patients with various arthritic conditions. Although Chronic Fatigue Syndrome (CFS) patients also experience pain, the diagnostic hallmark of their condition appears to be primarily fatigue. Over 75 percent of the symptoms from FM and CFS appear to overlap, and many medical authorities believe that FM and CFS are different manifestations of the same disease.
Prevalence of FM
At best, the prevalence of FM in the US is an educated guess based upon the number and percentage of patients diagnosed by rheumatologists. The prevalence ranges from two to five percent of the population or 2,500,000 to 15,000,000. Most authorities agree that women comprise 80 to 85 percent of FM cases. It has been suggested that a higher percentage of men may be afflicted, but they associate complaining of pain with weakness of character and therefore do not seek medical help. One might conclude from the high prevalence of women that FM is due to hormonal disturbances, but insufficient scientific data is available to suggest estrogen and/or progesterone play any role in the symptoms associated with FM. Just as there are many undiagnosed diabetics functioning in what appears to be a normal lifestyle, so too are there uncountable victims of FM who appear healthy from an external point of view but are suffering extreme pain without knowing the cause. This is extremely frustrating for FM victims who are often dismissed by their primary care physicians as hypochondriacs.
What Causes FM?
Now comes the $64,000 question (I know this dates me from a TV show that went off the air over 25 years ago). There are more theories than denominations of Baptists or varieties of Heinz. Each proponent claims to have the solution that is at least 75 percent effective. If true, 50 times the number of actual FM patients would have already been cured!
I’ve selected a list of the more plausible causes (Figure 4) and will discuss in some detail the merits of each.
In general, research has failed to show definitive differences in the anatomy, metabolism (at rest or during exercise) or physiology of muscle tissue at the cellular or subcellular level of fibros vs. normal control subjects. One notable exception is data from the University of Alabama showing a reduction in blood flow to three specific areas of the brain in fibros including the thalamus. Although this was not a universal finding, the suggestion that a lack of adequate oxygenation to this critical sensory receptor may precipitate an ischemic reaction of pain deserves further investigation.
Few deny that muscle pain is involved symptomatically and tends to exacerbate the feeling of overall pain. In a recent presentation at the American College of Sports Medicine, we proposed a symptomatic model that might be used to explain the involvement of muscle and inactivity in the pain response (Figure 5). Of course, this model does not attempt to explain the causative factors responsible for pain but indicates how inactivity may exacerbate pain, which then reduces further voluntary activity, causing a worsening of FM symptoms.
Dr. St.-Amand, an internist and endocrinologist at UCLA, has proposed a missing link in the biochemical chain of events in muscle tissue. According to his theory, excess phosphate accumulates at the mitochondria due to a defect in phosphate excretion level and may be responsible for the underproduction of ATP and subsequent pain upon exertion. Dr. St.-Amand has recommended taking guaifenisen, a cough expectorant, which he claims removes toxins and reduces pain. However, research studies using guaifenisen as the treatment modality failed to show any differences in pain response of fibros taking guaifenisen versus placebo and did not provide an explanation as to why certain regions experience pain to the exclusion of other locations.
One of the major characteristics of FM is sleep deprivation. More than 75 percent of fibros report lack of restorative sleep. Lack of adequate phase 4 sleep may prevent production of some key hormones (e.g., growth hormone) affecting restoration of normal muscle function. According to Moldofsky’s hypothesis, alpha wave intrusion on stage IV sleep prevents adequate regeneration of growth hormone. If true, then the liver will not be able to produce sufficient quantities of somatomedin C (or IGF-1), making it difficult for muscle to function properly. This was an exciting theory. However, data suggests that only 36 percent of FM patients demonstrate alpha wave intrusion, and healthy individuals who normally display a pattern of alpha intrusion do not suffer from the effects of FM.
A lack of adequate growth hormone (GH) has been labeled the culprit responsible for poor muscle function, lack of energy and fatigue. Bennett and coworkers observed a reduction of FM symptoms after GH injection in fibros. When they discontinued the injections the symptoms returned. It appears from these data that the hypothalamic control of GH release may be dysfunctional. However, other authors have not observed symptomatic improvements related to levels of GH.
Serotonin may play an active role in reversing many of the symptoms previously discussed. Low levels are associated with sleep problems, pain, depression, migraines, altered immune function, Raynaud’s phenomenon and irritable bowel syndrome. Also, serotonin may affect the hypothalamic-Pituitary-Adrenal (HPA) axis and cortisol levels. It was assumed that FM patients possessed low levels of serotonin since the symptoms described above were characteristic of FM. Unfortunately, inconsistent findings of low serotonin have been found among fibros.
Depression is one of the common features present in over 25 percent of fibros. Can FM be caused or influenced by depressive states? Epstein found that 67 percent of fibros have major lifetime depression and 22 percent have current psychiatric disorders, including neuroticism and hypochondriasis. He also discovered that current states of anxiety correlate with functional impairment. Yet, it has been argued that depression is an outcome of FM, associated with the frustration of a missed diagnosis and the anxiety that is related to unresolved pain. Most researchers have reached the conclusion that depression is not the cause, but may be the outcome of FM.
If you speak with fibros, they will often state that their condition was precipitated after a physical or emotional trauma in their lives. Whether or not the stress response elicited from a traumatic event can cause FM is uncertain. There have been reports that 20 percent of fibro patients report onset of FM after a traumatic event or chronic stress. We do know that chronic stress can affect our body’s response to stress through the brain and endocrine system. This sympathetic response is often termed the Hypothalamic-Pituitary-Adrenal (HPA) axis. In normal individuals, cortisol is released during times of stress. As the day wears on, these cortisol levels show a substantial reduction later in the afternoon and evening. Some research has shown cortisol levels among fibros remain elevated. However, this is not a universal response. Adler, however, failed to show any change in cortisol response when fibros were confronted with a metabolic stress (hypoglycemia). Rather, he showed a 30 percent reduction in ACTH (which is released from the brain to stimulate the production of cortisol) and epinephrine (a stress hormone released by the adrenal gland) response after subjecting FM clients to hypoglycemia. He found FM symptoms worsened inversely to the release of these hormones. In effect, as more sympathetic type hormones were released from the brain, greater amounts of cortisol were released by the adrenal gland.
But let’s get right down to the major complaint of fibros: pain. What has research shown to be the cause of pain? Russell measured the levels of substance P, believed to be a transmitter of pain (present in the cerebro-spinal fluid), and released in response to noxious substances, which stimulates the thalamus to sense pain. He found a significant percentage of fibros had three times the amount of substance P. Several studies have corroborated his findings, in intent, if not magnitude of the differences in levels of substance P among fibros vs. normals. In a study conducted at the University of Florida (Staud, unpublished data), normal and FM clients were blindfolded and asked to touch a warm plate. Over half of the FM subjects felt an exaggerated pain (i.e., extreme heat) compared to the normal subjects. The modulation of this pain may be related to the amount of substance P released. However, there are inherent obstacles in the measurement of substance P, including high cost of the analysis, and its practicality as a diagnostic tool, yet this approach does provide hope that a definitive tool may be soon identified that is closely associated with the characteristic definition of FM.
Although there are certainly many more theories presented by well-meaning scientists, physicians, therapists, chiropractors, nutritionists, and patients, most are conjecture and lack a true scientific design or represent untested testimonials. It’s time to try and tie together some of these hypothesis and come us with a coordinated explanation of what may cause FM.
With so many conflicting hypotheses, is there a coherent theory to explain the pain, fatigue and other symptoms experienced by at least 50 percent of fibros? Teitelbaum suggests that FM is a sleep disorder associated with hypothalamic and immune dysfunction along with poor nutrition. He and others suggest that various infections (yeast, sinus, parasites, and fungus) along with low adrenal and thyroid function can cause FM. He does admit, however, that FM may also be a cause of these dysfunctions as opposed to the other way around.
Bennett has put forth a compelling multi-factorial discussion of the etiology of FM. He suggests that the threshold for muscle trauma is experienced among fibros at low levels of activity due to one of several factors:
- Genetic predisposition
- Decreased levels of IGF-1
- Deconditioned muscles (i.e., a person avoids further activity leading to reduced muscle fitness and increased susceptibility to trauma)
Bennett further argues that the pain experienced by fibros, perhaps due to increased levels of substance P, inhibits restful sleep resulting in alpha wave intrusion during stage IV (delta wave) sleep, thus leading to extreme fatigue, reduced secretion of GH, inadequate release of IGF-1 from the liver, poor restoration of muscle tissue, less activity and this endless pattern recycles. If, indeed, substance P is the culprit that transmits pain to the thalamus, we still do not know why fibros demonstrate higher levels of this substance in response to low levels of noxious stimuli.
One interesting and new twist into both the causation and treatment of FM was reported at a recent fibromyalgia conference. Dr. Dan Heffez, a neurosurgeon who surgically operates to widen the cervical neurocanal of fibros, presented evidence that he claims demonstrates a narrowing in the cervical region or the medullary/cervical union. Dr. Heffez said that not everyone is a candidate for this surgical procedure, and he pointed out the need to pre-diagnose fibro patients with a careful neurological exam followed by an MRI of the affected region. He equates the symptoms experienced by eligible fibros to that experienced by patients suffering from cervical stenosis. He has indicated that over 50 percent of fibros undergoing this surgical procedure experience significant relief of pain, fatigue, sleep disorder and depression. This data has not yet been published and awaits scientific scrutiny.
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