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Fibromyalgia

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Fibromyalgia

Fibromyalgia (FM or FMS) is a chronic syndrome (constellation of signs and symptoms) characterized by diffuse or specific muscle, joint, or bone pain, fatigue, and a wide range of other symptoms. It is not contagious, and recent studies suggest that people with fibromyalgia may be genetically predisposed[1]. It affects more females than males, with a ratio of 9:1 by ACR (American College of Rheumatology) criteria[2]. Fibromyalgia is seen in 3% to 6% of the general population, and is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood. Because the nature of fibromyalgia is not well understood, some physicians believe that it may be psychosomatic or psychogenic[3]. Although there is no universally accepted cure, some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted[4]. The disease is not life-threatening, though the degree of symptoms may vary greatly from day to day with periods of flares (severe worsening of symptoms) or remission. The syndrome is generally perceived as non-progressive, yet that issue is still debated.[5] [6]

History

Fibromyalgia has been studied since the early 1800s and referred to by a variety of former names, including muscular rheumatism and fibrositis[7]. The term fibromyalgia was coined in 1976 to more accurately describe the symptoms, from the Latin word fibra, meaning fiber, and the Greek words myo,meaning muscle, and algos, meaning pain.

Fibromyalgia was first recognized by the American Medical Association as a true illness and the cause of disability in 1987. In an article the same year, in the Journal of the American Medical Association, a physician named Dr. Don Goldenberg called the syndrome Fibromyalgia.

Symptoms

The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to light touch, and usually moderate to severe fatigue. Those affected may also experience heightened sensitivity of the skin (also called allodynia), tingling of the skin (often needle-like), achiness in the muscle tissues, prolonged muscle spasms, weakness in the limbs, and nerve pain. Chronic sleep disturbances are also characteristic of fibromyalgia, and some studies suggest that these sleep disturbances are the result of a sleep disorder called alpha-delta sleep , a condition in which deep sleep (associated with delta EEG waves) is frequently interrupted by bursts of brain activity similar to wakefulness (i.e. alpha waves). Deeper stages of sleep (stages 3 &4) are often dramatically reduced.

In addition, many patients experience cognitive dysfunction (known as "brain fog" or "fibrofog"), which may be characterized by impaired concentration and short-term memory consolidation, impaired speed of performance, inability to multi-task, and cognitive overload [8]. Many experts suspect that "brain fog" is directly related to the sleep disturbances experienced by sufferers of fibromyalgia. However, the relationship has not been strictly established.

Other symptoms often attributed to fibromyalgia (possibly due to another comorbid disorder) may include Myofascial pain syndrome, chronic paresthesia, physical fatigue, irritable bowel syndrome, genitourinary symptoms (such as those associated with the chronic bladder condition interstitial cystitis), dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although it is common in people with fibromyalgia for pain to be widespread, it may also be localized in areas such as the shoulders, neck, back, hips, or other areas. Many sufferers also experience varying degrees of temporomandibular joint disorder. Not all patients have all symptoms.

Fibromyalgia can, but does not always, start as a result of some trauma (such as a traffic accident), major surgery, or disease. Some evidence shows that Lyme Disease is a common trigger of fibromyalgia symptoms.[9] However, there is currently no known strong correlation between any specific type of trigger and the subsequent initiation of symptoms. Symptoms can have a slow onset, and many patients have mild symptoms beginning in childhood, that are often misdiagnosed as growing pains. Symptoms are often aggravated by unrelated illness or changes in the weather. They can become more tolerable or less tolerable throughout daily or yearly cycles; however, many people with fibromyalgia find that, at least some of the time, the condition prevents them from performing normal activities such as driving a car or walking up stairs. The syndrome does not cause inflammation as is present in rheumatoid arthritis, although some anti-inflammatory treatments, such as Ibuprofen and Iontophoresis, may temporarily reduce pain symptoms in some patients.

Variability of Symptoms

The following factors have been proposed to exacerbate symptoms of pain in patients:

  • Increased psychosocial stress
  • Physical exertion (exercise seems to decrease the pain threshold of people with Fibromyalgia but increase it in healthy individuals[10])
  • Cold weather, especially when damp
  • Changes in barometric pressure
  • Lack of deep (stage 4) sleep

Diagnosis

Strictly speaking, there are no "diagnostic criteria" for the disorder. Rather, there exist a widely accepted set of classification criteria for research purposes which were elaborated in 1990 by the Multicenter Criteria Committee of the the American College of Rheumatology. These criteria, which are known informally as "the ACR 1990" define fibromyalgia according to the presence of the following criteria:

  • A history of widespread pain lasting more than three months — affecting all four quadrants of the body, i.e., both sides, and above and below the waist.
  • Tender points — there are 18 designated possible tender points (although a person with the syndrome may feel pain in other areas as well). During diagnosis, four kilograms-force (40 newtons) of force[8] is exerted at each of the 18 points; the patient must feel pain at 11 or more of these points for fibromyalgia to be considered. Four kilograms of force is about the amount of pressure required to turn fingernails white or to feel pain sensations on the forehead. This technique was developed by the American College of Rheumatology as a means of classifying an individual as having fibromyalgia for both clinical and research purposes. While these criteria for classification of patients were originally established as inclusion criteria for research purposes and were not intended for clinical diagnosis, they have become the de facto diagnostic criteria in the clinical setting. It should be noted that the number of tender points that may be active at any one time may vary with time and circumstance.

Objective Tests

Many people with fibromyalgia have abnormal autonomic function, which may be demonstrated by tilt table testing, which is an evaluation of autonomic function. In addition, several studies have demonstrated a reduction in heart rate variability (HRV) in patients with fibromyalgia, which may be interpreted as reflecting an increase in sympathetic tone or, alternatively, a decrease in parasympathetic tone. One interpretation of this phenomenon is that it may represent a less adaptive autonomic nervous system in response to physiological stressors.

Differentials

A number of other disorders can produce essentially the same symptoms as fibromyalgia. Other disorders known to produce similar symptoms are:

Treatment

As with many other disorders, there is no universal cure for fibromyalgia. However, a steady interest in the disorder on the part of academic researchers as well as pharmaceutical interests has led to improvements in its treatment, which ranges from symptomatic prescription medication to alternative and complementary medicine.

Traditionally, low doses of sedating antidepressants (e.g. amitriptyline and trazodone) have been used to reduce the sleep disturbances that are associated with fibromyalgia, which are believed by some practitioners to exacerbate the symptoms of the disorder. Because depression often accompanies chronic illness, these antidepressants may provide additional benefits to patients suffering from depression. Amitriptyline is often favoured as it can also have the effect of providing relief from neuralgenic or neuropathic pain. Some doctors advise against using narcotic sleep aids ("hypnotics"), since these can lead to dependence.

Another treatment being researched is the use of dextromethorphan, which is sold over the counter as a cough suppressant.[11]

Standard clinical doses of newer anti-depressants (SSRIs) like Celexa are being used. Anti-seizure drugs are also sometimes used.[citation needed]

New drugs that have shown significant efficacy in the treatment of fibromyalgia pain and other symptoms include milnacipran, gabapentin, and pregabalin. Milnacipran belongs to a new series of drugs known as serotonin-norepinephrine reuptake inhibitors (SNRIs) and is available in parts of Europe where it has been safely prescribed for other disorders. As of August 2005, Milnacipran is the subject of a Phase III study and, if ultimately approved by the FDA, will be distributed in the United States.

The newest drug for treating the extreme pain of Fibromyalgia is Lyrica, pregabalin, originally used for the nerve pain suffered by diabetics.

Studies have found gentle exercise, such as warm-water pool therapy, improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[citation needed] Stretching is recommended to allay muscle stiffness and fatigue, as is mild aerobic exercise. Because strenuous activity can exacerbate the muscle pain and fatigue already present, patients are advised to begin slowly and build their activity level gradually to avoid inducing additional pain. Exercise may be poorly tolerated in more severe cases with abnormal post-exertional fatigue.

Cognitive behavioral therapy has been shown to improve quality of life and coping in fibromyalgia patients and other sufferers of chronic pain.[citation needed]

Neurofeedback has also shown to provide temporary and long-term relief.[citation needed]

Many patients find temporary relief by applying heat to painful areas. Those with access to physical therapy and/or massage may find them beneficial. Chiropractic care can also help relieve pain due to fibromyalgia.[citation needed]

A holistic approach — including managing diet, sleep, stress, activity, and pain — is used by many patients. Dietary supplements, massage, chiropactic care,[citation needed] managing blood sugar levels, and avoiding known triggers when possible means living as well as it is in the patient's power to do.

Treatment for the "brain fog" has not yet been developed, however biofeedback and self-management techniques such as pacing and stress management may be helpful for some patients. The use of anti-depressants, which improves sleep, helps some patients, as does supplementation with folic acid and ginkgo biloba.[citation needed]

Among the more controversial therapies in common use among some patients involves the use of the expectorant guaifenesin. The use of this agent originated from the thoughts of Dr. R. Paul St. Amand, hence the name St Amand's protocol. Many patients report improvement on this treatment, which in turn has inspired health care providers to incorporate it in their practice. However, the efficacy of guaifenesin in treating fibromyalgia has not been proven in properly designed research studies. Indeed, a controlled study conducted by researchers at Oregon Health Science University in Portland failed to demonstrate any benefits from this treatment.

A number of practitioners are attracted to the treatment of fibromyalgia, especially because its cause has yet to be identified and, due to its permanent nature, ongoing treatments can be very profitable. While this interest may promote legitimate medical research, patients should be wary: Treatments of dubious validity exist in the meantime.

Living with fibromyalgia

Fibromyalgia can affect every aspect of a person's life. While neither degenerative nor fatal, the chronic pain associated with fibromyalgia is pervasive and persistent. FMS can severely curtail social activity and recreation, and as many as 30% of those diagnosed with fibromyalgia are unable to maintain full-time employment. Like others with disabilities, individuals with FMS often need accommodations to fully participate in their education or remain active in their careers.

In the United States, those who are unable to maintain a full-time job due to the condition may apply for Social Security Disability benefits. Although fibromyalgia has been recognized as a genuine, severe medical condition by the government, applicants are often denied benefits. However, most are awarded benefits at the state judicial level; the entire process often takes two to four years.

In the United Kingdom, the Department for Work and Pensions recognizes fibromyalgia as a condition for the purpose of claiming benefits and assistance[12].

Fibromyalgia is often referred to as an "invisible" illness or disability due to the fact that generally there are no outward indications of the illness or its resulting disabilities. The invisible nature of the illness, as well as its relative rarity and the lack of understanding about its pathology, often has psychosocial complications for those that have the syndrome. Individuals suffering from invisible illnesses in general often face disbelief or accusations of malingering or laziness from others that are unfamiliar with the syndrome.

There are a variety of support groups on the Web that cater to fibromyalgia sufferers. Some are offered at the bottom of this article.

Theories on the cause of fibromyalgia

The cause of fibromyalgia is currently unknown. Over the past few decades, many theories have been presented, and the understanding of the disorder has changed dramatically. Most current theories explain only a few symptoms of the disorder and are thus incomplete.

Genetics

Using self-report of "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry suggests a modest genetic contribution[13][14]:

  • Monozygotic twins with CWP have a 15% chance that their twin sibling has CWP
  • Dizygotic twins with CWP have a 7% chance that their twin sibling has CWP

Stress

Studies have shown that stress is a significant precipitating factor in the development of fibromyalgia[15], and that PTSD is linked with fibromyalgia.[16][17] The Amital study found that 49% of PTSD patients fulfilled the criteria for FMS, compared with none of the controls.

Dopamine abnormality

Dopamine is a neurotransmitter that is known to play a role in the pathogenesis of Parkinson's disease as well as restless leg syndrome. Pramipexole, a drug that stimulates dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless legs syndrome, has also been shown in controlled trials to have a positive effect on fibromyalgia. The National Fibromyalgia Association (NFA) recently circulated a press release describing a report [9] that appears in the January 2007 Journal of Pain article which reports that fibromyalgia patients demonstrate a significant reduction in dopamine synthesis in the very areas of the brain wherein dopamine plays a role in fighting painful bodily sensations (i.e. analgesia).

Serotonin

Serotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration, digestion. One hypothesis of the pathophysiology fibromyalgia causation is a dysregulation of serotonin and norepinephrine in the neural synapse, contributing to many associated fibromyalgia symptoms.

The drug Cymbalta, originally used to treat depression, has been used successfully in treating fibromyalgia off-label. Cymbalta has not been approved by the FDA for fibromyalgia.

On October 19 2006, Eli Lilly issued a press release stating they had done trials which found Cymbalta, 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia (FM), with and without major depression, according to 12-week data presented at the annual meeting of the American College of Rheumatology. Eli Lilly is in Phase III of its FM trials and is expected to submit a supplementary new drug application (sNDA) to the FDA for approval of Cymbalta for FM within the next 12 months.

Critics argue that randomized controlled trials of FM are difficult due to factors such as a lack of understanding of the pathophysiology and a heterogeneous FM patient population. Although there is a lack of understanding of what causes FM, it is estimated that approximately 5-7% of the U.S. population has FM,[18] representing a large patient clientèle. Eli Lilly hopes Cymbalta will be the first FDA approved medication for FM and had been promoting Cymbalta for FM since 2004[19].

In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study. Researchers also tested the participants for depression.

Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo. For men, who made up only 11 percent of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study.

However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the 12-week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time. Lastly, the primary researcher on the project has received more than $10,000 in consulting fees from Eli Lilly, the manufacturer of Cymbalta, all other researchers also had ties to the company, reflecting a conflict of interest.

For information on Cymbatla and FM you can visit the following site: "Role of Cymbalta in Fibromyalgia," Health-Care-Information.org [10]

Sleep disturbance

The sleep disturbance theory postulates that fibromyalgia is related to sleep quality. Electroencephalography (EEG) studies have shown that people with fibromyalgia lose deep sleep[20]. Circumstances that interfere with "stage 4" deep sleep (such as drug use, pain, depression, serotonin deficiency, or anxiety) appear to be able to cause or worsen the condition.

According to the sleep disturbance theory, an event such as a trauma or illness causes sleep disturbance and, possibly, some sort of initial chronic pain. These initiate the disorder. The theory supposes that "stage 4" sleep is critical to the function of the nervous system, as it is during that stage that certain neurochemical processes in the body reset. In particular, pain causes the release of the neuropeptide substance P in the spinal cord, and substance P has the effect of amplifying pain and causing nerves near the initiating ones to become more sensitive to pain. Under normal circumstances, this just causes the area around a wound to become more sensitive to pain, but, if pain becomes chronic and body-wide, then this process can run out of control. The sleep disturbance theory holds that deep sleep is critical in order to reset the substance P mechanism and prevent this out-of-control effect.

An interesting aspect of the sleep disturbance/substance P theory is that it explains "tender points" that are characteristic of fibromyalgia but which are otherwise enigmatic, since their positions don't correspond to any particular set of nerve junctions or other obvious body structures. The theory posits that these locations are more sensitive because the sensory nerves that serve them are positioned in the spinal cord to be most strongly affected by substance P. The theory also explains some of more general neurological features of fibromyalgia, since substance P is active in many other areas of the nervous system.

Critics of the theory argue that it does not explain slow-onset fibromyalgia, fibromyalgia present without tender points, or patients without heightened pain symptoms, and a number of the non-pain symptoms present in the disorder.

Also of interest is a possible connection between this theory and the theory that chronic fatigue syndrome and post-polio syndrome are due, at least in part, to damage to the ascending reticular activating system of the reticular formation. This area of the brain, in addition to apparently controlling the sensation of fatigue, is known to control sleep behaviors and is also believed to produce some neuropeptides, and thus injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia, explaining why the two disorders so often occur together.

Deposition disease

Another theory involves phosphate and calcium accumulation in cells that eventually reaches a level to impede the ATP process, possibly caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the blood stream. This theory posits that fibromyalgia is an inherited disorder, and that phosphate buildup in cells is gradual (but can be accelerated by trauma or illness). Calcium is required for the excess phosphate to enter the cells. The additional phosphate slows down the ATP process; however the excess calcium prods the cell to continue producing ATP[21].

Diagnosis is made with a specialized technique called mapping, a gentle palpitation of the muscles to detect lumps and areas of spasm that are thought to be caused by an excess of calcium in the cytosol of the cells. This mapping approach is specific to deposition theory, and is not related to the trigger points of myofascial pain syndrome.

While this theory does not identify the causative mechanism in the kidneys, it proposes a treatment known as guaifenesin therapy. This treatment involves administering the drug guaifenesin to a patient's individual dosage, avoiding salicylic acid in medications or on the skin, and, if the patient is also hypoglycemic, a diet designed to keep insulin levels low.

The phosphate build-up theory explains many of the symptoms present in fibromyalgia and proposes an underlying cause. The guaifenesin treatment, based on this theory, has received mixed reviews, with some practitioners claiming many near-universal success and others reporting no success. Only one controlled clinical trial has been conducted to date, and it showed no evidence of the efficacy of this treatment protocol. This study was criticized for not limiting the salicylic acid exposure in patients, and for studying the effectiveness of only guaifenesin, not the entire treatment method. As of 2005, further studies to test the protocol's effectiveness are in the planning stages, with funding for independent studies largely collected from groups which advocate the theory. It should be noted that nothing in the scientific literature supports the proposition that fibromyalgia patients have excessive levels of phosphate in their tissues.

Fibromyalgia as severe TMS

Another theory is that fibromyalgia is a severe form of Tension myositis syndrome (TMS) which is a mindbody disorder popularized in the books on healing back, neck, and other limb pain by Dr. John E. Sarno of the Howard A. Rusk Institute of Rehabilitation Medicine. Briefly the theory is that in many cases chronic pain is the result of physical changes (primarily mild oxygen deprivation) caused by the brain through the autonomic nervous system as a strategy for distracting you from painful or dangerous unconscious emotions such as repressed anger. Treatment is through a program of education and attitude change which stops the brain from using that chronic pain strategy. Psychotherapy is suggested in the minority of cases where education alone is not sufficient. [22] [23] [24]

Other theories

Other theories relate to various toxins from the patient's environment, viral causes such as the Epstein-Barr Virus, growth hormone deficiencies possibly related to an underlying (maybe autoimmune) disease affecting the hypothalamus gland, an aberrant immune response to intestinal bacteria,[25][26] neurotransmitter disruptions in the central nervous system, and erosion of the protective chemical coating around sensory nerves. A 2001 study suggested an increase in fibromyalgia among women with extracapsular silicone gel leakage, compared to women whose implants were not broken or leaking outside the capsule.[27] This association has not repeated in a number of related studies,[28] and the US-FDA concluded "the weight of the epidemiological evidence published in the literature does not support an association between fibromyalgia and breast implants."[29] Due to the multi-systemic nature of illnesses such as fibromyalgia and chronic fatigue syndrome (CFS/ME), an emerging branch of medical science called psychoneuroimmunology (PNI) is looking into how the various theories fit together.

Another hypothesis on the cause of symptoms in Fibromyalgia comes from new research that patients suffer from vasomotor dysregulation causing improper vascular and lymphatic drainage. This results in hypoperfusion - (Hypoperfusion being described as decreased blood flow to a given tissue or organ) It is thought that in FMS there is a disrupted flow of Lymphatic / Serous Fluids) body-wide. [30]This may be due to various causes and associated with the malfunction of the enzyme Hyaluronidase in degrading one of the body's glycosaminoglycans Hyaluronan. The natural flow of Serous Fluid (clear fluids called sera, plasma, interstitial and synovial fluids, spinal fluid, saliva, lymph, etc.) and its ability to leave the body via the lymphatic capillaries can become impaired. [31] Very recently a study conducted at Yale University School of Medicine entilted "The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation." has confirmed some of these findings. [11]

Comorbid diseases

Cutting across several of the above theories is a theory that proposes that fibromyalgia is almost always a comorbid disorder, occurring in combination with some other disorder that likely served to "trigger" the fibromyalgia in the first place. This concept fits especially well with the sleep disturbance theory.

By this theory, some other disorder (or trauma) occurs first, and fibromyalgia follows as a result. In some cases, the original disorder abates on its own or is separately treated and cured, but the fibromyalgia remains. This is especially apparent when fibromyalgia seems triggered by major surgery. In other cases the two disorders coexist. This theory would explain why such a wide variety of symptoms are often ascribed to fibromyalgia, since there are potentially a wide variety of comorbid disorders. It also helps explain why fibromyalgia is so hard to treat, since the fibromyalgia is unlikely to abate while the comorbid condition is untreated.

References

  1. ^ Information from the National Fibromyalgia Association
  2. ^ Fibromyalgia from WebMD
  3. ^ Sarno, John E., MD, Leonard-Segal, Andrea, MD, The Divided Mind: The Epidemic of Mindbody Disorders 2006 (ISBN 0-06-085178-3) pp. 21-22, 294-298
  4. ^ Leonard-Segal, Andrea, MD, The Divided Mind: The Epidemic of Mindbody Disorders 2006 (ISBN 0-06-085178-3) pp. 264-265, "I have successfully treated many patients who carry the diagnosis of fibromyalgia. ... It is almost as though those with fibromyalgia have so many issues from which the pain distracts them, that they accumulate pain in many locations as their defense mechanism. ... As with other TMS patients, those with fibromyalgia can be helped if they are open to considering and then accepting that there is a psychological cause for their pain. If they are unable to be open in this way, I have not been able to help them."
  5. ^ http://allexperts.com/ep/2520-20864/Fibromyalgia/Joyce-McKenzie.htm
  6. ^ http://www.med.ucla.edu/modules/wfsection/article.php?articleid=141
  7. ^ Fibromyalgia, published by BUPA insurance
  8. ^ Fibrofog, Fibromyalgia and Dissociation
  9. ^ Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia
  10. ^ Staud R, Robinson ME, Price DD (2005). "Isometric exercise has opposite effects on central pain mechanisms in fibromyalgia patients compared to normal controls". Pain. 118 (1–2): 176–84. PMID 16154700.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ [1] Cough syrup found by University of Florida to reduce fibromyalgia pain "moderately" but not recommended for personal self treatment.
  12. ^ The Fibromyalgia Association of the UK
  13. ^ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Importance of genetic influences on chronic widespread pain". Arthritis Rheum. 54 (5): 1682–6. doi:10.1002/art.21798. PMID 16646040.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Chronic widespread pain and its comorbidities: a population-based study". Arch. Intern. Med. 166 (15): 1649–54. PMID 16908799.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L (2000). "The impact of life events in female patients with fibromyalgia and in female healthy controls". Eur Psychiatry. 15 (5): 33–41. PMID 10954873. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Amital D, Fostick L, Polliack ML, Segev S, Zohar J, Rubinow A, Amital H (2006). "Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities?". J Psychosom Res. 61 (5): 663–9. PMID 17084145. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Raphael KG, Janal MN, Nayak S (2004). "Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women". Pain Med. 5 (1): 33–41. PMID 14996235. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ [2] National Fibromyalgia Association Brochure
  19. ^ [3] Duloxetine Effective in Fibromyalgia Arthritis Rheum. 2004;50:2974-2984
  20. ^ [4]
  21. ^ Are phosphates the hidden enemy? (76.7kb pdf)
  22. ^ Sarno, John E., MD The Mindbody Prescription: Healing the Body, Healing the Pain 1998 (ISBN 0-446-67515-6) pp. 76-78
  23. ^ Sarno, John E., MD The Divided Mind: The Epidemic of Mindbody Disorders 2006 (ISBN 0-06-085178-3) pp. 21-22,235-237,294-298
  24. ^ Selfridge, Nancy, MD, and Peterson, Franklynn Freedom from Fibromyalgia: The 5-Week Program Proven to Conquer Pain (2001) (ISBN 0-8129-3375-3) pp. 56-57
  25. ^ Kendall SN (2004). "Remission of rosacea induced by reduction of gut transit time". Clin Exp dermatol. 29 (3): 297–9. PMID 15115515. {{cite journal}}: Unknown parameter |month= ignored (help)
  26. ^ Pimental M, Wallace D, Hallegua D et .al (2004). "A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing". Ann Rheum Dis. 63 (4): 450–2. PMID 15020342. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Brown SL, Pennello G, Berg WA, Soo MS, Middleton MS (2001). "Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women". J Rheumatol. 28 (5): 996–1003. PMID 11361228 FDA Summary.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Lipworth L, Tarone RE, McLaughlin JK. (2004). "Breast implants and fibromyalgia: a review of the epidemiological evidence". Ann Plast Surg. 52 (3): 284–7. PMID 15156983.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ [5]
  30. ^ [6]
  31. ^ [7]
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