Fibromyalgia - Causes & Risk Factors

The cause of fibromyalgia remains unknown.

Identifying a single abnormality as the cause is difficult, in part, because fibromyalgia comprises a range of symptoms. Another difficulty is that fibromyalgia may not be caused by an external factor but instead may represent an underlying abnormality unmasked in some people by any one of several possible triggers. Triggers of fibromyalgia might include a flulike illness or a traumatic event, such as an auto accident, divorce, or the death of a family member.

Searching for the cause of fibromyalgia has led to controversy. Abnormalities have been found in people with fibromyalgia, but many questions for researchers remain: Is the abnormality the root cause of fibromyalgia, or is it the result of fibromyalgia? For instance, is depression the cause of fatigue, or is depression the result of constant pain? Is the difficulty in obtaining restful sleep the cause of symptoms, or is the pain the result of the stress accompanying this chronic illness?

Despite ongoing research, those particular questions lack definitive answers. Without a uniform abnormality certain cause, there can be no certain cure. And the lack of a cure frustrates many fibromyalgia patients.

In attempting to identify a cause, researchers have focused on several specific areas:

  1. The Role of Muscles
  2. The Role of Sleep
  3. Impact on the Immune System
  4. Neurohormones: The Role of Stress
  5. Effect of Increased Cortisol (Adrenal Gland)
  6. Sympathetic Nervous System and Neuropeptide Y
  7. Growth Hormone Deficiency’s Role
  8. Estrogen and Progesterone’s Role
  9. Thyroid Dysfunction
  10. Serotonin Abnormalities
  11. Pain Pathways
    • Normal Endorphin Levels
    • High Substance P Levels
    • Nervous System Sensitization
    • Alterations in the Brain
  12. Depression: Cause or Result
  13. A Cohesive Hypothesis of Pain

1. The Role of Muscles in Fibromyalgia

Past research has focused on abnormalities in muscles and muscle fibers because patients report muscular pain that tends to worsen with physical activity and have tender points that are usually found in muscle.

Studies that use control groups find few specific muscle abnormalities. One study in the Journal of Rheumatology finds normal muscle strength in fibromyalgia patients (1). Other research reported in Rheumatic Disease Clinics of North America notes normal muscle tension in fibromyalgia volunteers even though many complained of "tense" muscles (2).

There is general consensus among researchers that global muscle dysfunction muscle abnormalities in fibromyalgia patients can largely be attributed to disuse or to the muscles being out of shape, which is also referred to as deconditioning (3).

Though there does not appear to be a general defect in muscle tissue, there may be ways that the muscles and nervous system interact that exaggerate pain impulses. The resulting pain leads to disuse and deconditioning (4).

Section References

(1) "Isokinetic and isometric muscle strength combined with transcutaneous muscle stimulation in primary fibromyalgia syndrome," by S. Jacobsen et al, Journal of Rheumatology, Vol. 18, 1991, pages 1390-1393.

(2) "Is there muscle pathology in fibromyalgia syndrome?," by Robert Simms, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 245-266.

(3) "What is the future of fibromyalgia?," by D.L. Goldenberg, Rheumatic Disease Clinics of North America, Vol. 22, No. 2, May 1996, pages 393-406.

(4) “The contribution of muscle to the generation of fibromyalgia symptomatology,” by R.M. Bennett, Journal of Musculoskeletal Pain, Vol. 4, 1996, pages 35-59.

2. The Role of Sleep

As many as 75% of fibromyalgia sufferers report trouble sleeping (1). Some studies suggest an association between sleep disturbance and the development of fibromyalgia.

An early study in 1975, published in Psychosomatic Medicine, showed abnormal electroencephalogram patterns during non-REM sleep in fibromyalgia patients. Alpha waves, normally found during REM sleep, intruded during non-REM sleep in fibromyalgia subjects. When normal volunteers were deprived of non-REM sleep, they reported symptoms similar to fibromyalgia, but did not develop fibromyalgia (2).

However, alpha wave intrusion into non-REM sleep is not a consistent finding. A 1995 study showed that only 36 percent of fibromyalgia subjects have “alpha intrusion.” The study also reported that the presence of alpha intrusion does not correlate to disease severity. Nor is the intrusion unique to fibromyalgia; it has been found in healthy individuals and in those with other rheumatic conditions. The study reported further that amitriptyline had beneficial effects on non-REM sleep and thus alleviated or ameliorated the symptoms of fibromyalgia. But the reported improvement in symptoms in this study was the same for those with the EEG anomaly as for those without it (3).

Because of the important relationship between sleep, stress and hormonal changes, research into sleep dysfunction among fibromyalgia patients continues.

Section References

(1) "The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee," by F. Wolfe et al, Arthritis and Rheumatism, Vol. 33, No. 2, Feb. 1990, pages 160-172.

(2) "Musculoskeletal symptoms and non-REM sleep disturbance in patients with 'fibrositis syndrome' and healthy subjects," by H. Modolfsky, P. Scarisbrick, R. England, and H. Smythe, Psychosomatic Medicine, Vol. 37, 1975, pages 341-351.

(3) "Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia," by Simon Carette et al, Arthritis and Rheumatism, Vol. 39, No. 9, Sept. 1995, pages 1211-1217.

3. Impact on the Immune System

Researchers have investigated whether fibromyalgia is an autoimmune disorder, such as lupus or rheumatoid arthritis. The general consensus among researchers is that fibromyalgia is not an auto-immune disease.

Autoimmune disorders are defined by the presence of autoantibodies. Autoantibodies are abnormal antibodies created by the individual's body, which attack and damage normal tissue.

In a 1990 study, researchers measured the autoantibody levels in those with fibromyalgia who had not already been diagnosed for rheumatoid arthritis and thyroid disease. The result showed that those with fibromyalgia showed no greater chance of testing positive for autoantibodies than did a control group without fibromyalgia (1). The authors concluded that fibromyalgia is not primarily an autoimmune disorder.

Section References

(1) “Absence of autoantibodies in primary fibromyalgia," by A. Bengtsson, J. Ernerudh, M. Vrethem, and T. Skogh, Journal of Rheumatology, Vol. 17, 1990, pages 1682-1683.

4. Neurohormones -- The role of stress in fibromyalgia

Since the 1930s, when the word stress was coined to describe emotional challenges and psychic distress, researchers have delved into the relationship between stress and disease, including the link between stress and fibromyalgia.

Two findings indicate that stress may play a role in some fibromyalgia patients is likely to play a role in fibromyalgia. First, 20 percent of those diagnosed with fibromyalgia reported the onset of symptoms after a traumatic event, and second symptoms were worse following encounters with stress (1).

Two major components of the human body are designed to respond to and regulate stress: the hypothalamus-pituitary-adrenal axis (HPA axis) and the sympathetic nervous system.

Human stress responses can become dysfunctional if the stress is persistent and unrelenting. Chronic stress, a fact of life for many people today, can upset an individual's normal stress response and lead to illness that takes the shape of immune dysfunction, gastrointestinal upset, behavioral changes and altered perceptions of pain.

Some patients with fibromyalgia show changes in hormones including cortisol, epinephrine, norepinephrine, growth hormone, estrogen, progesterone, thyroid, and serotonin. However, it seems likely that these abnormalities are secondary to having fibromyalgia rather than a treatable cause for fibromyalgia.

Section References

(1) "Primary fibromyalgia, a clinical and laboratory study of 55 patients," by A. Bengtsson et al, Scandinavian Journal of Rheumatology, Vol. 15, 1986, pages 340-347.

5. The Role of Cortisol and the Adrenal Gland

A Journal of Rheumatology study published in 1992 found abnormalities with the regulation of cortisol in fibromyalgia patients (1). Normally, cortisol levels increase during times of stress, and imbalances in cortisol levels impede the body’s response to stress.

The hypothalamus-pituitary-adrenal axis (HPA axis) regulates the level of cortisol, a hormone, produced by the adrenal gland, that helps to control metabolism and moderate the immune system. Stress causes changes to the HPA axis, which leads to increased cortisol levels through a series of steps. Initially, stressful events induce the hypothalamus to produce cortisol-releasing hormone (CRH) and arginine vasopressin (AVP). CRH and AVP then act on the anterior pituitary, a structure beneath the hypothalamus, to release adrenocorticotropic hormone (ACTH). Finally, ACTH promotes the production of cortisol by the adrenal gland. Once levels of cortisol reach a certain point, the hormone acts on receptors back in the brain to prevent further production of CRH and AVP.

Just as a thermostat can be set at various levels, the point at which production of more CRH is stopped can vary. Laboratory experiments with rats showed that stressful experiences early in life can alter this set point (2). The influence of early life experiences on later hormonal function is assumed to apply to humans as well.

A Journal of Rheumatology study showed a group of fibromyalgia patients secreted higher than normal levels of ACTH when administered CRH (3). A later study reported that the adrenal gland of patients with fibromyalgia responded to administration of CRH with lower than normal levels of cortisol. The same study showed that fibromyalgia patients have lower levels of urinary cortisol excretion. This finding suggests reduced adrenal gland secretion of cortisol excretion (4).

Cortisol levels in the blood normally fluctuate throughout the day, with high levels in the early morning and low levels in the evening. Another study reported that in some fibromyalgia patients there is a loss in the normal evening decline in cortisol, as would be expected in a stress response (5).

These findings represent a complex alteration of adrenal hormone regulation. Researchers are intrigued because the results in those studies point to an association between fibromyalgia, a stress-related illness, and levels of cortisol, one of the hormones related to biological stress. This dysfunction is intricately related to other hormonal changes observed in fibromyalgia patients, such as with serotonin and growth hormone.

Section References

(1) "Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome," by L. Crofford, and M.A. Demitrack, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 267-283.

(2) "Environmental regulation of the development of glucocorticoid receptor systems in the rat forebrain," by M.J. Meaney et al, Annals of the New York Academy of Science, Vol. 746, 1994, pages 260-273.

(3) "Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome," by E. Griep, J. Boersma, and E.R. de Kloet, The Journal of Rheumatology, Vol. 20, No. 3, 1993, pages 469-473.

(4) "Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia," by L. Crofford, S. Pillemer et al, Arthritis and Rheumatism, Vol. 37, No. 11, Nov. 1994, pages 1583-1592.

(5) "Loss of diurnal variation in serum cortisol, growth hormone and prolactin in patients with primary fibromyalgia," by K. Tilbe, D.A. Bell, and G.A. McCain, Arthritis and Rheumatism, Vol. 33 (supplement), 1988, page S99.

6. Sympathetic Nervous System and Neuropeptide Y

Individuals with fibromyalgia have lower levels than normal of a component of the sympathetic nervous system called neuropeptide Y. Researchers have yet to determine the effect of the lower levels.

The sympathetic nervous system responds to stress by inducing what is commonly referred to as the "fight or flight" response, which includes such physiological changes as increased heart rate, increased blood pressure and changes in metabolism. The changes are mediated through the chemicals epinephrine (adrenaline) and norepinephrine and through small, chemically active proteins that act on the nervous system, called neuropeptides.

Several studies showed fibromyalgia subjects have normal levels of epinephrine and norepinephrine in the plasma and urine (1). However, a study published in Arthritis and Rheumatism showed a neuropeptide released upon activation of the sympathetic system is lower in the plasma of fibromyalgia patients (2). Researchers have not determined the clinical implications of lower neuropeptide production.

One study has postulated that the neuropeptide, called neuropeptide Y, influences the hypothalamus-pituitary-adrenal (HPA) axis activity. The research was unable to determine whether the low levels seen in the blood corresponds to levels in the brain, nor did investigators find the reason people with fibromyalgia have lower plasma levels of neuropeptide Y. The authors, however, pointed out that exercise stimulates the production of neuropeptide Y and that low levels could be due to the decreased activity levels common to those with fibromyalgia (3).

Section References

(1) "Plasma and urinary catecholamines in primary fibromyalgia: A controlled study," by M.B. Yunus et al, Journal of Rheumatology, Vol. 19, 1992, pages 95-97.

(2) "Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia," by L. Crofford, S. Pillemer et al, Arthritis and Rheumatism, Vol. 37, No. 11, Nov. 1994, pages 1583-1592.

(3) "Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome," by L. Crofford, and M.A. Demitrack, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 267-283.

7. Growth Hormone Deficiency’s Role

A study showed fibromyalgia patients are deficient in growth hormone and its mediator in tissues, somatomedin-C. Researchers proposed the deficiency may be related to sleep dysfunction, lack of physical activity, or abnormalities in the hypothalamus-pituitary-adrenal axis (HPA) axis.

The study compared serum levels of somatomedin-C in 70 fibromyalgia patients to 55 healthy controls and found that the average level of somatomedin-C is significantly lower in fibromyalgia patients. The growth hormone is produced by the pituitary and promotes the liver's production of somatomedin-C (often referred to as insulin-like growth factor 1 or IGF-1), which influences the growth of muscles and bones.

A deficiency of the IGF-1 in fibromyalgia patients may result from dysfunctional sleep because the growth hormone secretion peaks during non-REM sleep. Somatomedin C's role in the body is to regulate normal muscle metabolism and growth, therefore, low levels of it lessen the ability of the muscle to repair itself after physical exertion. The lack of repair can lead to persistent muscular pain. The study's authors proposed that sleep dysfunction could lead to muscle aches because the dysfunction disrupts the secretion of growth hormone and somatomedin C.

The study pointed out also that growth hormone in fibromyalgia patients could be decreased because exercise induces growth hormone secretion. The majority of fibromyalgia patients reported decreased daily activity, and that, in turn, could lead to a reduction in somatomedin C levels (1).

Another study, published in the Journal of the American Medical Association, hypothesized that the deficiency may stem from interactions within the HPA axis. the growth hormone's complex interaction with the HPA axis. Cortisol-releasing hormone (CRH) from the hypothalamus can enhance somatostatin secretion (2). Somatostatin in turn inhibits the secretion of growth hormone by the pituitary gland. This represents a potential link between stress and growth hormone levels.

Section References

(1) "Low levels of somatomedin C in patients with the fibromyalgia syndrome: A possible link between sleep and muscle pain," by R. Bennett, S. Clark, S. Campbell and C. Burckhardt, Arthritis and Rheumatism, Vol. 35, No. 10, Oct. 1992, pages 1113-1116.

(2) "The concept of stress and stress system disorders: Overview of physical and behavioral homeostasis," G.P. Chrousos, P.W. Gold, Journal of the American Medical Association, Vol. 267, No. 9, March 4, 1992, pages 1244-1252.

8. Estrogen and Progesterone’s Role

The observations that women are more likely to have fibromyalgia than men and that more women report fibromyalgia symptoms after menopause suggest the hormones estrogen and progesterone may play a role in fibromyalgia.

Laboratory evidence showed estrogen alters the hypothalamus-pituitary-adrenal axis (HPA) axis, which is related to the body’s management of stress. Conversely, disruption of the HPA axis can change patterns of estrogen and progesterone secretion, according to a study in Rheumatic Disease Clinics of North America (1).

The two reports cited above show how estrogen and progesterone could influence the course of fibromyalgia. The interaction is complicated, and researchers lack a clear explanation of why both the presence of these hormones during early adulthood and the loss of them after menopause would increase a woman's likelihood of suffering fibromyalgia.

Section References

(1) "Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome," by L. Crofford, and M.A. Demitrack, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 267-283.

9. Thyroid Dysfunction

Thyroid dysfunction can lead to fatigue, cognitive changes, alterations in sleep and diffuse muscle aching similar to fibromyalgia. But standard tests for thyroid dysfunction have been consistently normal in those fibromyalgia patients without known thyroid disease. Hypothyroid patients with fibromyalgia who are adequately treated for hypothyroidism still have fibromyalgia.

In 1992, a Journal of Rheumatology study found subtle alterations in thyroid function in fibromyalgia patients. Despite production of normal amounts of thyroid hormone, the thyroid gland in the study's subjects did not respond normally to hormonal stimulation. The authors proposed that the lack of normal response was related to alterations of cortisol (1) These abnormalities are probably part of a stress response, and not a cause for fibromyalgia symptoms, according to Bennett.

The implications of the finding are unknown. What is known is that fibromyalgia patients with normal thyroid levels should not use thyroid hormone supplements.

(1) "Thyroid function in patients with fibromyalgia syndrome," by G. Neeck and W. Riedel, Journal of Rheumatology, Vol. 19, No. 7, 1992, pages 1120-1122.

10. Serotonin Abnormalities

Blood serotonin levels and metabolism have been reported as abnormal in people with fibromyalgia, as shown in a 1996 Rheumatic Disease Clinics of North America study (1). However, this has not been found by all investigators (2).

The abnormality is important because serotonin, a neurotransmitter, serves many functions in the body. Changes in serotonin levels lead to physiological changes that overlap remarkably with fibromyalgia symptoms: sleep problems, widespread pain, depression, migraine headaches, altered immune function, Raynaud's phenomenon and irritable bowel syndrome.

Depressed patients have lower levels of serotonin by-products in their spinal fluid. Migraine headaches are thought to be due to local changes of serotonin within the brain. Serotonin has also been shown to alter the function of various components of the immune system. And, altered serotonin levels are associated with Raynaud’s phenomenon and irritable bowel syndrome (3).

Seratonin became a key suspect as a cause of fibromyaliga in 1982 (4). Further research showed that serum concentrations of serotonin in fibromyalgia patients were lower than normal (5) Another study, published in the journal Pain, showed that although tryptophan levels remained within the normal range in the study's subjects, there is an inverse relationship between levels of tryptophan, the amino acid precursor to serotonin, and fibromyalgia symptoms (6) This means a decrease in tryptophan correlated to an increase in symptoms.

Another study, in Arthritis and Rheumatism, reported that compounds related to serotonin metabolism were lower in the spinal fluid of people with fibromyalgia (7). Because serotonin is also known to interact with the HPA axis, the finding means serotonin may play a role in altering cortisol regulation.

The association of altered serotonin levels and fibromyalgia is also supported by the finding that drugs, such as antidepressants, alter serotonin levels in the brain and often improve fibromyalgia symptoms. Research into the role of serotonin and methods to control serotonin levels continues.

Section References

(1) "Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome," by Leslie Crofford and M.A. Demitrack, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 267-283.

(2) "Plasma tryptophan and other amino acids in primary fibromyalgia syndrome: a controlled study, M.B. Yunus, J.W. Dailey, J.C. Aldag, A.T. Masi, P.C. Jobe, Journal of Rheumatology, vol. 19, 1992, pages 90-94.

(3) “Neurohormonal aspects of fibromyalgia syndrome," by I.J. Russell, Rheumatic Disease Clinics of North America, The Fibromyalgia Syndrome, Vol. 15, No. 1, Feb. 1989, pages 149-168.

(4) "Rheumatic pain modulation syndromes: The interrelationships between sleep, central nervous system, serotonin and pain," by H. Moldofsky, Adv Neurology, Vol. 33, 1982, pages 51-57 (as cited in "Neurohormonal aspects of fibromyalgia syndrome," by I.J. Russell, Rheumatic Disease Clinics of North America, The Fibromyalgia Syndrome, Vol. 15, No. 1, Feb. 1989, pages 149-168.)

(5) "Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia," by L. Crofford, S. Pillemer et al, Arthritis and Rheumatism, Vol. 37, No. 11, Nov. 1994, pages 1583-1592.

(6) "Plasma tryptophan and musculoskeletal pain in non-articular rheumatism ("fibrositis syndrome")," by H. Moldofsky and J.J. Warsh, Pain, Vol. 5, 1978, pages 65-71.

(7) "Cerebrospinal fluid biogenic amines in fibrositis/fibromyalgia syndrome," I.J. Russell, H. Vaeroy, and M. Javors, Arthritis and Rheumatology, Vol. 33 (supplement) 1990, page S55.

11. Pain Pathways

Researchers have investigated whether the aching pain and discomfort of fibromyalgia results from a change in the manner in which the central nervous system perceives pain. Alterations in nervous system function could result in individuals experiencing severe pain from otherwise mild or moderate stimulus. What seems like a bothersome sensation to someone without fibromyalgia, could feel like intolerable pain to someone with fibromyalgia because of changes in the way the nervous system functions.

The sensation of pain from muscle is transmitted via specialized pain fibers to the spinal cord where they transmit the signal by releasing substance P and other active compounds. From there the signal is relayed to the thalamus, a nucleus deep within the brain, and then onto the sensory cortex, where pain sensation reaches consciousness. The perception of pain could be altered at any point along the pathway.

  • Normal Endorphin Levels
  • High Substance P Levels
  • Nervous System Sensitization
  • Alterations in the Brain

Normal Endorphin Levels

Evidence suggests people with fibromyalgia have normal levels of endorphins.

Endorphins are a class of neuropeptides (small, chemically active proteins that act on the nervous system) created by the body to reduce pain. Stressful or painful events promote the production of endorphins to mitigate pain. Opiates, such as morphine, are chemically related, and their use has the same effect as endorphins.

Because of the profound, persistent nature of the pain in fibromyalgia patients, researchers have investigated whether the pain is due to a deficiency of endorphins. A study in the 1986 Journal of Rheumatology showed that serum endorphin levels in people with fibromyalgia are normal (1). Another report, in the same journal in 1988, showed fibromyalgia patients also have normal endorphin levels in the fluid surrounding the brain, the cerebrospinal fluid (2).

Despite the normal findings thus far, some researchers speculate there are focal variations within specific regions of the brain. Current limitations in testing prevent them from confirming the hypothesis.

Section References

(1) "Serum beta-endorphin in primary fibromyalgia syndrome: A controlled study," by M. Yunus, C. Denko, and A. Masi, The Journal of Rheumatology, Vol. 13, No.1, 1986, pages 183-186.

(2) "Cerebrospinal fluid levels of beta-endorphin in patients with fibromyalgia (fibrositis syndrome)," by H. Vaeroy, R. Helle et al, Journal of Rheumatology, Vol. 15, No. 12, 1988, pages 1804-1806.

High Substance P Levels

Painful stimuli trigger the release of substance P via sensory nerve fibers. Substance P is a neuro-transmitter, an important relay of pain impulses to the brain. A 1988 Journal of Rheumatology study showed that levels of substance P in the blood of fibromyalgia patients are normal (1).

In some studies, fibromyalgia subjects had abnormally high levels of substance P in their spinal fluid. In people without fibromyalgia, injection of substance P into the spinal cord can elicit a painful sensation. This suggests that the nervous systems of people with fibromyalgia may transmit pain in an abnormal way.

A 1994 report in Arthritis and Rheumatism showed that substance P levels in the spinal fluid are three times greater in fibromyalgia patients than in normal controls (2). This finding supports the idea that fibromyalgia patients have an up-regulated pain sensation system, which means that fibromyalgia patients would feel otherwise normally innocuous sensations as pain. The authors pointed out that their finding could be related also to other neurologic abnormalities, such as changes in serotonin levels.

Section References

(1) "Elevated CSF levels of substance P and haigh incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis,” H. Vaeroy, R. Helle, O. Forre, E. Kass, L. Terenius, Pain, vol. 32, 1988, pages 21-26.

(2) "Elevated cerebrospinal fluid levels of substance P in patients with fibromyalgia syndrome," by I.J Russell et al, Arthritis and Rheumatism, Vol. 37, No. 11, 1994, pages 1593-1601.

Nervous System Sensitization

One theory is that the pain experienced by those with fibromyalgia may be due to increased sensitization caused by exposure to persistent pain (1).

It is well-documented that persistent pain can lead to changes within the brain and spinal cord that serve to lower the pain threshold. With the changes, the same source of discomfort seems even more painful when it is experienced again.

An article in the journal Pain says that pain in one region of the body may be perceived in adjacent areas due to local changes in the spinal cord. This experimental evidence explains why some people who suffer pain in an isolated area later develop generalized pain. The Scandinavian Journal of Rheumatology reported that as many as 87 percent of fibromyalgia sufferers first have localized symptoms (2).

The theory of increased sensitization is still just speculation and is not supported by any specific clinical evidence in fibromyalgia patients.

Section References

(1) "Review article: Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence," by T. Coderre, J. Katz, A. Vaccarino, and R. Melzack, Pain, Vol. 52, 1993, pages 259-285.

(2) "Primary fibromyalgia. A clinical and laboratory study of 55 patients," by A. Bengtsson et al, Scandinavian Journal of Rheumatology, Vol. 15, 1986, pages 340-347.

Alterations in the brain

In an attempt to determine whether changes in pain are due to abnormalities within the brain, researchers studied two components of the pain pathway, the thalamus and caudate nucleus.

Using a sophisticated radiologic test called single photon-emission computed tomographic imaging (SPECT), they assessed the blood flow to these two structures in the brain. Their results, published in a 1995 issue of Arthritis and Rheumatism, showed that blood flow to the thalamus and caudate nucleus is decreased in patients with fibromyalgia. The authors hypothesized that the functional abnormality could be related to the low pain thresholds seen in fibromyalgia patients (1).

Findings are preliminary, and further studies are under way to assess functional changes within the structures of the pain pathway.

Section References

(1) "Fibromyalgia in women: Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain thresholds levels," by J. Mountz et al, Arthritis and Rheumatism, Vol. 38, No. 7, July 1995, pages 926-938.

12. Depression: Cause or Result?

Perhaps no topic causes greater controversy than the discussion surrounding the association of depression and fibromyalgia.

On one side of the issue, classic psychosomatic theory claims psychological conflict can lead to the development of physical symptoms, and the medical profession has long held the belief that depression could give rise to fibromyalgia. Patients with major depression frequently have some symptoms of fibromyalgia and associated problems, such as fatigue, poor concentration, migraine headaches, and irritable bowel syndrome.

Evidence of a link between fibromyalgia and depression comes from a landmark Kansas study of 3,006 people that found those with a history of depression were four times more likely to have fibromyalgia symptoms (1). A review article in Rheumatic Disease Clinics of North America said fibromyalgia patients respond to psychological tests similar to patients with major depression (2).

On the other side of the issue, an American Journal of Medicine study noted that depression frequently develops after fibromyalgia symptoms appear (3). In addition, the symptoms commonly found among fibromyalgia and depressed patients appear in no particular order. For instance, irritable bowel syndrome may appear either before or after the onset of fibromyalgia.

A comprehensive article in the May 1996 issue of Rheumatic Disease Clinics of North America concluded depression does not cause fibromyalgia nor does fibromyalgia cause depression. Instead, the article said, both are caused by an underlying factor and are thus closely linked. The authors stated that numerous investigators have all arrived at the conclusion that fibromyalgia and major depressive disorders are probably parts of a wider spectrum of related disorders. Research has yet to define how the disorders are interwoven (4).

Section References

(1) "The prevalence and characteristics of fibromyalgia in the general population," by F. Wolfe et al, Arthritis and Rheumatism, Vol. 38, No. 1, pages 19-28.

(2) "The relationship between fibromyalgia and major depressive disorder," by J. Hudson and H.G. Pope, Rheumatic Disease Clinics of North America, Controversies in Fibromyalgia and Related Conditions, Vol. 22, No. 2, May 1996, pages 285-303.

(3) "Co-morbidity of fibromyalgia, medical and psychiatric disorders," by J.I. Hudson, D.L. Goldenberg et al, American Journal of Medicine, Vol. 92, 1992, pages 363-367.

13. A Cohesive Hypothesis of Pain

A 1996 study in the Journal of Musculoskeletal Pain brings together various proposed causes of fibromyalgia to create a cohesive explanation. The study shows how various factors are interrelated, including sleep dysfunction, growth hormone deficits, deconditioning and changes in the nervous system's response to pain (1).

The authors speculated that excessive physical activity induces microscopic trauma to the muscle, referred to as microtrauma. What is considered "excessive" may vary from person to person with fibromyalgia sufferers having especially low thresholds of activity-induced damage, making them especially vulnerable to microtrauma. The muscle injury is exacerbated by eccentric contractions of the muscles, which occur when the limb extends while the muscle is contracting. For example, an eccentric contraction takes place in your arms when you slowly set down a bag of groceries. Tenderness and stiffness, as well as malaise, mark the injury one to two days after it occurs.

Fibromyalgia patients, could be particularly sensitive and susceptible to microtrauma for three reasons: a potential genetic predisposition; decreased levels of somatomedin C, which inhibits the proper repair of damaged; and muscles that are deconditioned or out of shape.

As the pain of microtrauma recurs, two things happen. First the person avoids further activity, resulting in worsening muscle fitness and increased susceptibility to further microtrauma. Second, the persistent pain may sensitize the pain pathways causing each event to be increasingly painful and perceived in more extensive regions of the body.

Persistent pain often inhibits restful sleep and alters the person’s sleep pattern, including the EEG changes of alpha intrusion. Poor sleep is probably a major determinant of the severe fatigue experienced by most fibromyalgia patients. Lack of restful sleep also leads to decreased growth hormone and somatomedin-C secretion. The result is further decline in the muscle's ability to repair itself after injury. And, the resulting fatigue from loss of sleep leads to a further decrease in physical activity.

The proposed mechansims shows how all the proposed causes of fibromyalgia, outlined above, may in fact be intimately interrelated. It also supports the idea that there is no single cause to fibromyalgia.

Effective treatment for fibromyalgia patients must thus aim toward improving several aspects of life, including sleep management, fitness, pain control, and stress reduction.

Section References

(1) “The contribution of muscle to the generation of fibromyaliga symptomatology,” R.M. Bennett, Journal of Musculoskeletal Pain, vol. 4, 1996, pages 35-59.

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