Fibromyalgia Case Study

affectinhg young to middle-aged women.1 Fibromyalgia has a varied and fluctuating clinical spectrum. The symptoms of Fibromyalgia are musculoskeletal pain and tenderness, sleep issues and significant levels of fatigue. The other key symptoms include cognitive disturbances, particularly problems with concentration, memory, and high distress levels.2 Fibromyalgia can be considered part of a group of clinical syndromes, including chronic fatigue syndrome, multiple chemical sensitivities and irritable bowel syndrome, whose clinical features reflect similar pathophysiological processes – termed by some as ‘central sensitivity syndromes’.3 These different diagnoses are used depending on the predominant clinical features. For example, patients
with fatigue as their most severe symptom may receive a diagnosis of chronic fatigue syndrome.
Fibromyalgia has been thought to be caused by the development of changes in the central nervous system (CNS)4,5 that alter the processing of afferent sensory input, and can be grouped together under the term ‘central sensitisation’.6 Central sensitisation changes are often triggered by long-standing psychological or physical stress.7 These changes result in the intensity of usually non-painful stimuli being amplified and experienced as painful. Other effects include abnormality in the sleep cycle, where patients are unable to achieve deep, restorative, stage IV non-REM sleep, and disturbances in the hypothalamic-pituitary axis, with altered levels of serum cortisol, decreased 24-hour urinary free cortisol and blunted cortisol responses to dynamic testing.8
Genetic polymorphisms resulting in alteration in CNS serotonergic and catecholaminergic processes continue to be investigated, and appear to increase the risk of developing fibromyalgia.9
Aside from any genetic predisposition, clinical fibromyalgia is frequently triggered. In an internet survey of 2 596 fibromyalgia patients in North America, 79% described potential triggering events at the onset of the their fibromyalgia,10 while 88.7% of patients seen in an Australian public hospital fibromyalgia clinic reported recognisable triggers.11 A physical or psychological stressor in a susceptible individual can result in a chronic, maladaptive stress response, which, in turn, mediates the central changes.12
Fibromyalgia is diagnosed according to criteria published by the American College of Rheumatology (ACR). The initial classification criteria were published in 1990 and included widespread musculoskeletal pain and tenderness measured by the ‘tender point count’ on physical examination.13 These criteria was useful in defining a standard group for research purposes, however it did not and does not recognize the broader spectrum or fluctuating nature of fibromyalgia symptoms.
In 2010 the ACR published diagnostic criteria, taking these aspects into consideration.14 This criteria now accounts for chronic musculoskeletal pain, as well as fatigue, sleep problems, cognitive disturbance and other symptoms. In publishing this criteria, the authors recognised that fibromyalgia symptoms fluctuate significantly over time and they aimed to be able to recognise a spectrum of severity in patients with central sensitisation symptoms – rather than just those with the most severe illness who satisfied the traditional definition of fibromyalgia. The severity scale captured by the new criteria has been termed by some as a degree of ‘fibromyalgianess’ or a ‘polysymptomatic distress scale’.15,16 Recent research focus uses this gauge of central sensitisation symptom severity to investigate the extent of sensitisation syndrome features in patients with fibromyalgia, chronic pain and other associated conditions.16 It is clear, however, that many clinical features of central sensitisation are also found in a large number of other chronic illnesses.
The diagnosis of fibromyalgia is often not initially considered. In a large North American survey, 46% of fibromyalgia patients had consulted 3–6 health care providers regarding their symptoms, prior to their fibromyalgia diagnosis.10
When should fibromyalgia be considered?
Fibromyalgia has multiple, varied and fluctuating symptoms. It should be considered when a patient describes chronic musculoskeletal pain, fatigue and poor sleep. These symptoms are usually accompanied by a number of other problems such as depression or anxiety, sensitivity to chemicals, irritable bowel or restless legs. The symptoms often start or worsen during a period of severe psychosocial or physical stress.
The key symptoms of fibromyalgia are also commonly found in many other illnesses, and a thorough examination and investigation needs to be undertaken in order to ensure there is not another pathological cause for the symptoms – particularly if there are any ‘red flags’ in the patient’s history suggestive of another serious pathology (Table 1).
• Older age at new symptom onset
• Weight loss
• Night pain
• Focal pain
• Fever or sweats
• Neurological features
• History of malignancy
Care also needs to be taken when interpreting results of investigations, particularly radiology. Sometimes abnormalities found on musculoskeletal imaging are attributed to causing symptoms, when the clinical picture is much more global.
Often, screening questions based on the modified 2010 ACR criteria17 (Figure 1) are useful. If patients presenting with widespread chronic pain are also experiencing fatigue, sleep problems, cognitive disturbance, depression, headache and/or abdominal pain, then fibromyalgia should be considered Figure 1. New modified ACR diagnostic criteria for fibromyalgia17

When is fibromyalgia easy to miss?
Fibromyalgia is easy to miss when it coexists with another chronic illness, particularly when it occurs with another condition causing similar symptoms such as arthritis, endocrine disorders, depression or sleep apnoea.
Fibromyalgia coexists in a significant proportion of patients with rheumatoid arthritis. These patients have worse disease activity, joint tenderness and swelling, and psychological distress.18,19 Concomitant fibromyalgia is also reported in patients with systemic lupus erythematosis and osteoarthritis, who have significantly higher proportion of problems associated with central sensitisation, including sleep disturbance and fatigue.20–22 In these conditions, there is an obvious source of nociceptive input to drive central sensitisation processes. In a subgroup of patients with diabetes there is reported coexisting central sensitisation,23 and a significant proportion of patients with hyperthyroidism also have features of fibromyalgia.24 In all of these situations of chronic illness, the possibility of long-standing physical or psychological stress exists, so that even when there is no obvious nociceptive input (such as in thyroid disease), these patients can still develop the changes of central sensitisation. Therefore, if patients have clinical features out of keeping with general disease activity, then it may be necessary to consider whether central sensitisation could be contributing.
Management of fibromyalgia

Fibromyalgia is a complex disorder, requiring input from many different health care providers, including medical, allied health, and complementary and alternative medicine practitioners. General practitioners are in an ideal position to co-ordinate and monitor these multidisciplinary management strategies.
In this vulnerable patient group, psychosocial issues often arise. General practitioners are uniquely placed to recognise problems such as financial hardship, social isolation, loss of role and secondary depression, and can provide essential structured support and validation for these patients.
Education
Following fibromyalgia diagnosis, an in-depth discussion of the clinical features and pathological mechanisms of fibromyalgia is essential. Patient understanding of the condition and their expectations as to clinical improvement are key to developing a successful management program. Often the validation and reassurance experienced once a diagnosis is made result in improvement.25
The chronic and fluctuating nature of fibromyalgia and the management goals of symptom reduction and optimising function need to be explained. The importance of adherence to treatment plans and realistic expectations regarding progress and outcomes need ongoing reinforcement. Thorough and targeted patient education also results in increased patient engagement and proactive attitude to self management.
Psychology
A number of psychological interventions are helpful in the management of fibromyalgia. Concomitant depression and anxiety often occur in fibromyalgia, and can contribute significantly to reduced patient wellbeing. Addressing these problems, if present, is essential to any improvement in a patient’s overall health.
Stress management techniques are an essential part of any fibromyalgia therapeutic plan and, when combined with the development of other skills such as planning, pacing and coping strategies as part of cognitive behaviour therapy (CBT), then there is demonstrated improvement in pain-related behaviour, self-efficacy and physical function.26 Other psychological strategies such as mindfulness techniques may also be helpful. Mindfulness-based therapies seem to be effective in alleviating symptoms common in fibromyalgia such as pain, depression and a range of other psychological factors as well as improving health-related quality of life, although in studies with active comparator arms, they have in general, not proven superior.27,28 A recent randomised controlled trial of an online mindfulness intervention targeting socioemotional regulation in fibromyalgia patients resulted in significant improvement in social functioning, positive affect and coping efficacy for pain and stress.29
Exercise
Regular exercise improves pain, fatigue and sleep disturbance in patients with fibromyalgia.30 There is no ‘best’ form of exercise and all types may be considered. Aerobic exercise, in particular, reduces fibromyalgia symptoms and improves physical capacity.31 The initiation of any regular exercise program needs to be slow and gradual. Patients who are deconditioned and concerned regarding the possible worsening of pain and fatigue will need reassurance; they may need to start with only a few minutes of gentle exercise several times a week. This can be built up very slowly and gradually as tolerance increases. Often a hydrotherapy pool is a good place to start an exercise regimen, as the warmth of the water and relative weightlessness relieves symptoms while the resistance provides a gentle workout.
Other physical therapies
Other physical therapies can be helpful in the management of fibromyalgia, particularly those that can be self administered. There is evidence to support the use of yoga, qi gong and tai chi in patients with fibromyalgia.32 Studies in which the use of these therapies resulted in improvement in fibromyalgia symptoms and physical functioning were generally small and unblinded, however, given the lack of serious adverse effects and the promotion of self-efficacy, these management modalities are generally useful options.
Medication
Simple analgesia is often the first medication patients with fibromyalgia will trial. Guidelines published by the European League Against Rheumatism (EULAR) recommend the use of simple analgesics like paracetamol in the management of fibromyalgia; however, due to insufficient data this is based on expert opinion alone.33 Paracetamol use has not been studied in fibromyalgia patients, other than in combination with tramadol, where the combination resulted in a modest (18%) improvement in pain compared with placebo.34
Other studies have found some benefit with tramadol use for fibromyalgia;5,35 the therapeutic benefit was possibly due to tramadol’s serotonin-noradrenaline reuptake inhibition, rather than µ-opioid activity. Other opioid use in fibromyalgia is not routinely recommended. There is reduced opioid receptor availability in patients with fibromyalgia,36 and a lack of supportive evidence for their efficacy.37
The use of non-steroidal anti-inflammatory agents (NSAIDs) has not been supported with significant research data, however they are often used and a survey of 1042 patients with fibromyalgia, found that 66.1% deemed NSAIDs more effective than paracetamol.38
Antidepressants as pain modulators
Medications that elevate levels of serotonin and noradrenaline in the descending inhibitory nociceptive pathways of the CNS, such as low-dose tricyclic antidepressants (TCAs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), can provide significant benefit in patients with fibromyalgia independent of effects on mood.39 Amitriptyline, duloxetine and milnacipran are the best-studied agents in these categories, and all have substantial evidence for the significant improvement of pain, and other symptoms of fibromyalgia, although some early studies were short term.4 Milnacipran is approved by the Australian Therapeutic Goods Administration for use in fibromyalgia,40 but is not currently available in Australia.
Membrane stabilisers
Pregabalin and gabapentin bind to voltage-dependent calcium channels, reducing calcium influx into sensitised spinal cord neurons in central pain syndromes such as fibromyalgia. In a meta-analysis of randomised, controlled trials in fibromyalgia patients, the use of these agents resulted in reduced pain, improved sleep and better quality of life.41

Fibromyalgia affects 1% to 5% of Americans, mainly women, but until recently, scientists had no idea what might be causing its severe and mysterious pains. For decades, doctors told patients their agony was imaginary, the result of emotional hysteria, not a physical ailment.
But this year, researchers finally began to get a handle on the condition.
"What 's happened is in 2013 there 's been this absolute explosion of papers," says neurologist Anne Louise Oaklander at Massachusetts General Hospital in Boston. "The whole view on this has shifted."
Oaklander published two studies this year showing that half or more of the cases of fibromyalgia are really a little-known condition affecting the nerves.
People with this small-fiber neuropathy get faulty signals from tiny nerves all over the body, including internal organs, causing an odd constellation of symptoms from pain to sleep and digestive problems that overlap with symptoms of fibromyalgia.
Neuroscientist Frank Rice and a team based at Albany Medical College also discovered that there are excessive nerve fibers lining the blood vessels of the skin of fibromyalgia patients — removing any doubt that the condition is physically real.
These fibers in the skin can sense blood flow and control the dilation and constriction of vessels to regulate body temperature, Rice says, as well as direct nutrients to muscles during exercise. Women have more of these fibers than men, he says, perhaps explaining why they are much more likely to get fibromyalgia.
"Blood vessel nerve fibers are an important target that haven 't been in our line of thinking to date in chronic pain conditions," says Rice, now president and chief scientist at Integrated Tissue Dynamics LLC, a biotechnology research company in Rensselaer,
N.Y.
In recent years, scans of patients with fibromyalgia have revealed brain changes associated with pain, but the new research suggests these are a symptom rather than the cause of the condition.
This new understanding of fibromyalgia will hopefully lead to better treatments, Rice and Oaklander say.
Right now, most people are treated with the antidepressants Cymbalta made by Eli Lilly, or Savella by Forest Pharmaceuticals, or with Lyrica, a seizure medication from Pfizer — which have all been federally approved for use in fibromyalgia.
But these drugs have side effects and don 't help everyone.
We 're looking now to understand more about other features of the pathology that might lead to a more targeted approach and less of a shotgun that causes side effects," says Rice, also an adjunct professor at the University at Albany, State University of New York.
The trigger for fibromyalgia is still a mystery, although stressful events in patients ' past have been thought to play a role. However, there is some preliminary evidence that the nerve damage is caused by the immune system.
"We 're hoping some day we 'll be able to say exactly how your It has been thought that the immune system could be causing damage to the sensory nerves that results in fibromyalgia pain. Researchers don 't yet know whether the pain causes the other problems of fibromyalgia — disrupting sleep, for instance — or whether both pain and sleep disturbances share the same cause.
Fibromyalgia 's constellation of symptoms is very similar to those of chronic fatigue syndrome to the extreme as Gulf War syndrome. If someone has more of one symptom than another they might call it one thing such as chronic fatigue, but it 's not clear that these are different.

Researchers still have a lot to learn about these conditions, but scientists are taking them more seriously and making real progress for the first time.
New Canadian guidelines for treating fibromyalgia
Physicians from the McGill University Health Centre (MUHC) and the University of Calgary have published a review article in the CMAJ (Canadian Medical Association Journal) to help family doctors diagnose and treat fibromyalgia. The article represents the first time researchers have published Canadian guidelines to help manage the condition.

"One million Canadians have fibromyalgia and the time has come to take their suffering seriously. This is a real condition that greatly impacts patients and their families. Finally there are national guidelines to help diagnose and treat this syndrome," says Dr. John Pereira, a study co-author from the University of Calgary 's Faculty of Medicine and a physician at the Calgary Chronic Pain Centre.

Fibromyalgia is usually diagnosed by rheumatologists but due to the high prevalence of the disease many patients are not able to seek advice from a specialist. Therefore, primary care physicians are best positioned to take over this role, as recommended by the 2012 Canadian Fibromyalgia Guidelines. In the review, the authors provide evidence-based tools for primary care physicians to make the diagnosis and manage the condition long-term.
"We are the first ones to develop guidelines that look at diagnosis, treatment and follow-up of fibromyalgia," says Dr. Mary-Ann Fitzcharles, corresponding author from the Research Institute of the MUHC and MUHC 's rheumatologist. "Currently, there is no cure for fibromyalgia but the guidelines set out the most appropriate management strategy."
Authors recommend non-pharmaceutical interventions such as exercise, relaxation techniques, cognitive behavioral therapy as well as medications tailored to the individual patient. The main treatment goal is to improve quality of life by alleviating the most troublesome symptom(s), with pain recognized as the most common and serious.

Researchers are touting a “breakthrough discovery” in the diagnosis of fibromyalgia – a complex and painful condition that affects millions of people around the world.
In a new study being published in Pain Medicine, the journal of the American Academy of Pain Medicine, researchers based at Albany Medical College say they may have finally found the first biological evidence of what causes fibromyalgia.

“Instead of being in the brain, the pathology consists of excessive sensory nerve fibers around specialized blood vessel structures located in the palms of the hands,” said Frank Rice, PhD, President of Integrated Tissue Dynamics LLC (Intidyn) and the senior researcher on the study.
In a small study of fibromyalgia patients, researchers found an “enormous increase” in sensory nerve fibers in the blood vessels of the skin on the patients’ palms. The extra nerve fibers appear to disrupt the normal flow of blood, which may explain why many fibromyalgia patients often complain of tenderness or pain in their hands and feet.
“We previously thought that these nerve endings were only involved in regulating blood flow at a subconscious level, yet here we had evidence that the blood vessel endings could also contribute to our conscious sense of touch… and also pain,” said Rice.
“This discovery provides concrete evidence of a fibromyalgia-specific pathology which can now be used for diagnosing the disease, and as a novel starting point for developing more effective therapeutics.”
Fibromyalgia is a poorly understood disorder that is characterized by joint pain, deep tissue pain, fatigue, headaches, depression and lack of sleep. It affects about 10 million Americans, and one in 20 people worldwide. The underlying cause of fibromyalgia has confounded physicians for decades.
To analyze the nerve endings, Rice and his colleagues used microscopic technology to study small skin biopsies collected from the palms of fibromyalgia patients. The study was limited to women, who have over twice the occurrence of fibromyalgia than men. Image courtesy of Frank L. Rice, PhD, Integrated Tissue Dynamics, LLC
The team found the extra sensory nerve fibers in tiny muscular valves or “shunts,” which form a direct connection between arterioles and venules, the blood vessels in the
skin.
The shunts essentially act as thermostats, regulating body heat. Under warm conditions, the shunts close down to force blood into the capillaries of the skin in order to radiate heat away from the body. Under cold conditions, the shunts open wide, allowing blood to bypass the capillaries in order to conserve heat.
“The excess sensory innervation may itself explain why fibromyalgia patients typically have especially tender and painful hands. But, in addition, since the sensory fibers are responsible for opening the shunts, they would become particularly active under cold conditions, which are generally very bothersome to fibromyalgia patients,” said Dr. Charles Argoff, an Albany Medical Center neurologist and pain specialist, who was the study’s primary investigator.
Although they are mostly limited to the hands and feet, researchers say the shunts could have another important function which could account for the widespread pain, achiness, and fatigue that occurs in fibromyalgia patients.
“An enormous proportion of our blood flow normally goes to our hands and feet. Far more than is needed for their metabolism” noted Dr. Rice. “As such, the hands and the feet act as a reservoir from which blood flow can be diverted to other tissues of the body, such as muscles when we begin to exercise.”
“Therefore, the pathology discovered among these shunts in the hands could be interfering with blood flow to the muscles throughout the body. This mismanaged blood flow could be the source of muscular pain and achiness, and the sense of fatigue which are thought to be due to a build-up of lactic acid and low levels of inflammation (in) fibromyalgia patients.”
Reaction to the study from fibromyalgia experts was mixed.
“It is exciting that something has finally been found.” said Dr. Gary Bennett, Senior Research Chair of the Alan Edwards Center for Pain Research at McGill University. “We can hope that this new finding will lead to new treatments for fibromyalgia patients who now receive little or no relief from any medicine.”
“A great deal more research is indicated, but this is a good start. Loss of thermostatic control is a major complaint for many fibromyalgia patients, myself included,” said Celeste Cooper, RN, a patient advocate and author of Broken Body, Wounded Spirit: Battling the See-Saw of Chronic Pain.
“I hope they also screened the participants for the presence of myofascial trigger points. These knotted up pieces of muscle fiber can restrict blood flow, even in the smallest of vessels,” Cooper said in an email to National Pain Report. ”Many FM patients have a disorder called Raynaud’s disease or phenomenon where their hands, feet, nose, and sometimes ears turn blue when exposed to cold. They become numb and very painful on re-warming at which time, the color turns red. This is thought to result from spasm of the same vessels studied here.”
“Certainly, there is more than a casual connection of myofascial pain syndrome and Raynaud’s, but I am uncertain that fibromyalgia is a sympathetic nervous system disorder. We just need more research and consideration of comorbid disorders.”

Key points
• Fibromyalgia is a clinical syndrome resulting from a process of CNS sensitisation.
• It has varied and fluctuating symptoms and can be confused with other illnesses with similar features.
• Fibromyalgia can also coexist with other disorders, and identifying the source of clinical complaints can be difficult.
• The possibility of central sensitisation should be considered in all patients with chronic illness when the one particular aspect (particularly musculoskeletal pain or fatigue) is not responding to seemingly adequate treatment.

References
1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995;38:19–28. Search PubMed
2. Arnold LM, Clauw DJ, McCarberg BH. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc 2011;86:457–64. Search PubMed
3. Yunus MB. Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin Arthritis Rheum 2008;37:339–52. Search PubMed
4. Hauser W, Petzke F, Sommer C. Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. J Pain 2010;11:505–21. Search PubMed
5. Bennett RM, Schein J, Kosinski MR, Hewitt DJ, Jordan DM, Rosenthal NR. Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen. Arthritis Rheum 2005;53:519–27. Search PubMed
6. Clauw DJ, Arnold LM, McCarberg BH. The science of fibromyalgia. Mayo Clin Proc 2011;86:907–11. Search PubMed
7. Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states–maybe it is all in their head. Best Pract Res Clin Rheumatol 2011;25:141–54. Search PubMed
8. Crofford LJ, Engleberg NC, Demitrack MA. Neurohormonal perturbations in fibromyalgia. Baillieres Best Pract Res Clin Rheumatol 1996;10:365–78. Search PubMed
9. Buskila D. Developments in the scientific and clinical understanding of fibromyalgia. Arthritis Res Ther 2009;11:242. Search PubMed
10. Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord 2007;8:27. Search PubMed
11. Guymer EK, Maruff P, Littlejohn GO. Clinical characteristics of 150 consecutive fibromyalgia patients attending an Australian public hospital clinic. Int J Rheum Dis 2012;15:348–57. Search PubMed
12. Becker S, Schweinhardt P. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res Treat 2012;2012:741746. Search PubMed
13. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72. Search PubMed
14. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010;62:600–10. Search PubMed
15. Wolfe F. New American College of Rheumatology criteria for fibromyalgia: a twenty-year journey. ibid. 2010;62:583–84. Search PubMed
16. Wolfe F, Hassett AL, Katz RS, Michaud K, Walitt B. Do we need core sets of fibromyalgia domains? The assessment of fibromyalgia (and other rheumatic disorders) in clinical practice. J Rheumatol 2011;38:1104–12. Search PubMed
17. Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011; 38:1113–22. Search PubMed
18. Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum 2009;61:794–800. Search PubMed
19. Wolfe F, Hauser W, Hassett AL, Katz RS, Walitt BT. The development of fibromyalgia–I: examination of rates and predictors in patients with rheumatoid arthritis (RA). Pain 2011;152:291–99. Search PubMed
20. Morand EF, Miller MH, Whittingham S, Littlejohn GO. Fibromyalgia syndrome and disease activity in systemic lupus erythematosus. Lupus 1994;3:187–91. Search PubMed
21. Gladman DD, Urowitz MB, Gough J, MacKinnon A. Fibromyalgia is a major contributor to quality of life in lupus. J Rheumatol 1997;24:2145–48. Search PubMed
22. Hawker GA, French MR, Waugh EJ, Gignac MA, Cheung C, Murray BJ. The multidimensionality of sleep quality and its relationship to fatigue in older adults with painful osteoarthritis. Osteoarthritis Cartilage 2010;18:1365–71. Search PubMed
23. Yanmaz MN, Mert M, Korkmaz M. The prevalence of fibromyalgia syndrome in a group of patients with diabetes mellitus. Rheumatol Int 2012;32:871–74. Search PubMed
24. Soy M, Guldiken S, Arikan E, Altun BU, Tugrul A. Frequency of rheumatic diseases in patients with autoimmune thyroid disease. Rheumatol Int 2007;27:575–77. Search PubMed
25. Sim J, Madden S. Illness experience in fibromyalgia syndrome: a metasynthesis of qualitative studies. Soc Sci Med 2008;67:57–67. Search PubMed
26. Bernardy K, Fuber N, Kollner V, Hauser W. Efficacy of Cognitive-Behavioral Therapies in Fibromyalgia Syndrome – A Systematic Review and Metaanalysis of Randomized Controlled Trials. J Rheumatol 2010;37:1991–2005. Search PubMed
27. Carlson LE. Mindfulness-based interventions for physical conditions: a narrative review evaluating levels of evidence. ISRN Psychiatry 2012;2012:651583. Search PubMed
28. Schmidt S, Grossman P, Schwarzer B, Jena S, Naumann J, Walach H. Treating fibromyalgia with mindfulness-based stress reduction: results from a 3-armed randomized controlled trial. Pain 2011;152:361–69. Search PubMed
29. Davis MC, Zautra AJ. An Online Mindfulness Intervention Targeting Socioemotional Regulation in Fibromyalgia: Results of a Randomized Controlled Trial. Ann Behav Med 2013 [Epub ahead of print]. Search PubMed
30. Fitzcharles MA, Ste-Marie PA, Goldenberg DL, et al. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: Executive summary. Pain Res Manag 2013;18:119–26. Search PubMed
31. Busch AJ, Barber KA, Overend TJ, Peloso PM, Schachter CL. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2007;4:CD003786. Search PubMed
32. Mist SD, Firestone KA, Jones KD. Complementary and alternative exercise for fibromyalgia: a meta-analysis. J Pain Res 2013;6:247–60. Search PubMed
33. Carville SF, Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis 2008;67:536–41. Search PubMed
34. Bennett RM, Kamin M, Karim R, Rosenthal N. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med 2003;114:537–45. Search PubMed
35. Biasi G, Manca S, Manganelli S, Marcolongo R. Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo. Int J Clin Pharmacol Res 1998;18:13–19. Search PubMed
36. Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci 2007;27:10000–06. Search PubMed
37. Ngian GS, Guymer EK, Littlejohn GO. The use of opioids in fibromyalgia. Int J Rheum Dis 2011;14:6–11. Search PubMed
38. Wolfe F, Zhao S, Lane N. Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Arthritis Rheum 2000;43:378–85. Search PubMed
39. Perrot S, Javier RM, Marty M, Le Jeunne C, Laroche F. Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies. Rheumatology (Oxford) 2008;47:1117–23. Search PubMed
40. Therapeutic Goods Administration. Australian Public Assessment Report for Milnacipran. Available at: www.tga.gov.au/pdf/auspar/auspar-joncia.pdf [Accessed 9 August 2013].
41. Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of fibromyalgia syndrome with gabapentin and pregabalin – a meta-analysis of randomized controlled trials. Pain 2009;145:69–81. Search PubMed