Fibromyalgia patients are often concurrently diagnosed with restless leg syndrome (RLS). According to estimates, thirty to seventy percent of fibromyalgia patients also meet the diagnostic criteria for RLS, making it one of the primary comorbidities of fibromyalgia syndrome.⁽¹⁾⁽²⁾ Given this prevalence, it is constructive for fibromyalgia patients to develop an understanding of RLS and it’s relationship to fibromyalgia syndrome, including:

• similarities in clinical presentation/diagnosis
• possible common etiologies
• overlap of treatment modalities
• future trends

RLS Clinical Presentation/Diagnosis

Restless leg syndrome is a sensorimotor disorder causing unpleasant sensations and an almost irresistible urge to move the legs.⁽³⁾ The diagnostic criteria for RLS were established by the International Restless Legs Syndrome Study Group in 1995, and identify four essential components, along with several supportive and associated clinical features.⁽⁴⁾ The four essential components are:

1. Urge to move the legs
   -This is usually accompanied by uncomfortable or unpleasant sensations in the legs.
2. Onset or exacerbation with rest
   -The urge to move becomes more pronounced during periods of inactivity such as sitting or lying.
3. Relief with movement
   -The urge to move and unpleasant sensations are diminished by activity, for at least as long as the movement continues.
4. Circadian pattern
   -The urge to move is more pronounced in the evenings or night than during the day.

Disturbed sleep is the most common clinical manifestation of RLS and is often the primary reason patients seek medical attention. It should be noted, that while fibromyalgia patients also suffer from disturbed sleep patterns, RLS does not appear to be the root cause and sleep disturbances in fibromyalgia patients often occur in the absence of RLS.⁽⁵⁾ However, RLS sleep disturbances do appear to exacerbate the fatigue and cognitive impairment already present in many fibromyalgia patients.⁽²⁾

As with fibromyalgia syndrome, the vast majority of patients diagnosed with RLS are women, and there appears to be a strong hereditary component to both disorders.⁽²⁾ Additionally, some research indicates a genetic linkage between RLS, mood disorders and irritable bowel syndrome – three of the most common comorbidities of fibromyalgia syndrome.⁽⁶⁾⁽⁷⁾ Unfortunately, no laboratory test or physical exam can confirm the diagnosis of either fibromyalgia or restless leg syndrome, so timely and accurate diagnosis of each condition depends largely on the expertise of the health care provider.

Causes

The clinical study of RLS has mirrored that of fibromyalgia syndrome in the sense that researchers initially focused on possible peripheral causes but eventually concluded that CNS mechanisms were responsible for both syndromes. Current research suggests it is likely that both syndromes share a similar pathogenesis arising from dysfunction in the neuroendocrine system.⁽¹⁾ The exact mechanism of this CNS dysfunction is unclear, but it appears both pathologies involve increased spinal cord excitability and decreased regulation of sensory processing pathways.⁽⁸⁾⁽⁹⁾.

Much of the current fibromyalgia research is centered around the neurotransmitters, serotonin and norepinephrine, and the role they play in regulating pain.⁽⁸⁾ RLS research, meanwhile, has been primarily focused on dopamine, a neurotransmitter responsible for regulating motor control. Interestingly, recent evidence suggests that dopamine is also involved in pain modulation, indicating that, like restless leg syndrome, fibromyalgia may involve a disturbance of dopaminergic neurotransmission.⁽¹⁰⁾
.

Treatments

Fibromyalgia syndrome and RLS are treated with both pharmacologic and non-pharmacologic therapies. Non-pharmacologic therapies, like improved nutrition and better sleep hygiene, typically address functional symptoms of the disorders, while pharmacologic therapies usually act on neuroendocrine function in the central nervous system.⁽¹¹⁾

Drugs that increase levels of dopamine (i.e. ropinirole and pramipexole) are first-line treatments for restless leg syndrome.⁽³⁾ The majority of patients treated with these agents show improved symptoms, at least initially, but these medications can sometimes cause an augmentation, or rebound, effect and actually make symptoms worse between doses. This is especially likely to happen with older medications like levodopa. Attention should be paid to this possibility whenever initiating therapy or adjusting doses.⁽¹²⁾

It is also important to be aware that anti-depressant drugs used in the treatment of fibromyalgia can aggravate RLS symptoms in some patients, so a period of trial-and-error might be required to find appropriate therapies for an individual.⁽⁶⁾

Future

It appears that a combination of external environmental stressors and internal neuroendocrine dysfunction in genetically predisposed individuals leads to alterations in central nervous system function in both RLS and fibromyalgia syndrome.⁽³⁾⁽⁸⁾ Currently, the studies of both syndromes are directed primarily at neuroendocrine dysfunction and are likely to remain so for the foreseeable future. As the study of genetics continues to unravel the pathogenesis of fibromyalgia and RLS, the therapies should become more targeted toward specific, dysfunctional sensory pathways, leading to decreased symptoms and an improved quality of life.

Learn more about fibromyalgia at: www.myalganex.com

1. Yunus MB, Aldag JC. Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study. BMJ. 1996 May 25;312(7042):1339. [↩] [↩]
2. Stehlik R, Arvidsson L, Ulfberg J. Restless legs syndrome is common among female patients with fibromyalgia. Eur Neurol. 2009;61(2):107-11. Epub 2008 Dec 9. [↩] [↩] [↩]
3. Thomas K, Watson CB. Restless legs syndrome in women: a review. J Womens Health (Larchmt). 2008 Jun;17(5):859-68. [↩] [↩] [↩]
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5. Moldofsky H. The significance, assessment, and management of nonrestorative sleep in fibromyalgia syndrome. CNS Spectr. 2008 Mar;13(3 Suppl 5):22-6.
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7. Weinstock LB, Fern SE, Duntley SP. Restless legs syndrome in patients with irritable bowel syndrome: response to small intestinal bacterial overgrowth therapy. Dig Dis Sci. 2008 May;53(5):1252-6. Epub 2007 Oct 13. [↩]
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9. Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97. [↩]
10. Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007 Jun;25(12):3576-82. [↩]
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Fibromyalgia syndrome (FMS) is primarily a disorder of sensory amplification in which heightened sensory input causes a complex array of symptoms, including pain, fatigue, insomnia, and mood disorders.⁽¹⁾ This broad range of clinical manifestations can make fibromyalgia syndrome difficult to treat and usually requires a multi disciplinary approach to therapy. A rational therapeutic plan will target both the underlying sensory amplification disorder and the resultant functional symptoms.

The study of pain pathways is an area of great interest for fibromyalgia researchers, and along with genetics, provides significant hope for advancement in the diagnosis and treatment of FMS. Current research indicates that dysfunctional sensory amplification can occur via several neurochemical pathways, and treatment modalities usually involve pharmacologic manipulation of these neurochemicals.

Recently, much of the focus has been centered on the serotonin-norepinephrine descending pain pathway.⁽²⁾ In this pain processing pathway, serotonin and norepinephrine are used by the brain as intermediaries to inhibit pain signals from the body. Deficiencies of serotonin or norepinephrine cause this feedback mechanism to misfire, and pain processing signals remain unregulated.

This has sparked interest among clinicians because some studies indicate that serum levels of serotonin and norepinephrine are diminished in fibromyalgia patients. Subsequent clinical trials with medications that modulate serotonin and norepinephrine (i.e. amitriptyline, duloxetine, venlafaxine) have proven beneficial to some subjects.⁽³⁾⁽⁴⁾

Another area of active research involves the voltage-dependant calcium channel which controls the release of excitatory neurotransmitters involved in pain processing, including glutamate and substance P. Inhibiting the release of these compounds decreases pain signal processing. Pregabalin and gabapentin are the two primary medications of this class used in fibromyalgia patients.

One of the more troubling aspects of developing effective treatments is the idea that fibromyalgia syndrome can affect more than one pain processing pathway, and further, the pathways involved may not be the same for each patient. So, a medication that works reasonably well in one patient may be completely ineffective (or detrimental) in another.

Genetic research into fibromyalgia even raises the possibility of multiple etiologies for FMS. Several different genetic markers are under study, and it is possible that not a single gene, but a variable combination of genes, is responsible for the expression of fibromyalgia syndrome.^(5)(6)(7)(8) Simply stated, the root cause of fibromyalgia may not be the same for all patients.

Because the currently available treatments for primary pain provide incomplete relief, attention also must be given to treating the functional symptoms of fibromyalgia syndrome. The treatment of pain amplification disorder is almost exclusively the domain of pharmacology, but the broad nature of related functional symptoms invites the use of many treatment modalities, both pharmacologic and non-pharmacologic.

It is easy to imagine how a pain amplification disorder like fibromyalgia syndrome could cause otherwise sub-clinical ailments to become symptomatic and require treatment. For instance, a headache in a hypersensitized fibromyalgia patient might be experienced as intolerably painful, while the same headache in a person with normal pain processing pathways might be perceived as only a nuisance.

Of course, this is an oversimplification. The connection between fibromyalgia and other conditions (like depression) involves both genetics and endocrinology, and is not just a result of heightened pain sensations, but the point is that fibromyalgia syndrome has the potential to adversely effect virtually any system in the body.

Treatment of these functional symptoms is primarily symptomatic or palliative in nature, and since not everyone has the same symptoms, the treatment must be individualized. This variability accounts, at least in part, for the numerous testimonials and miracle cures found online. It may be possible to virtually eliminate a particular functional symptom of fibromyalgia without correcting the underlying pathology. Confusion arises when this is mistaken as a “cure” for fibromyalgia syndrome.

Some of the more popular treatment modalities for these functional symptoms include:

• Pharmacologic agents
• Education
• Cognitive Behavioral Therapy
• Nutrition & Dietary Supplements
• Biofeedback
• Exercise Programs
• Therapeutic Yoga
• Massage Therapy
• Acupuncture
• Electro therapy

It is important to remember that the treatment must be individualized when addressing these symptoms. Therapies will not always have the same effect on individual fibromyalgia patients. The only way to arrive at a truly optimized treatment plan is through trial-and-error. Understanding this before treatment begins should help fibromyalgia patients keep a positive attitude while sorting through the broad collection of available treatments.

Due to the variable etiology and expression of fibromyalgia syndrome, finding effective treatments can be difficult. Dividing treatment goals into two categories- reduction of primary pain amplification, and reduction of resulting functional symptoms- can clarify the procedure, and allow for the individualized development of an optimal therapeutic plan.

Learn more about fibromyalgia at: www.myalganex.com

1. Lawson K. Treatment options and patient perspectives in the management of fibromyalgia: future trends. Neuropsychiatr Dis Treat. 2008 Dec;4(6):1059-71. [↩]
2. Senba E, Imbe H, Okamoto K. Descending facilitation in chronic stress and chronic pain state. Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Feb;28(1):29-35. [↩]
3. Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992 May;35(5):550-60. [↩]
4. Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis. JAMA. 2009 Jan 14;301(2):198-209. [↩]
5. Bondy et al. The T102c polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol. Dis. 1999;6:433-439. [↩]
6. Offenbaecher et al. Possible association of fibromyalgia with a polymorphism in the seratonin transporter gene regulatory region. Arthritis Rheum. 1999;42:2482-2488. [↩]
7. Buskilla et al. An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking behavior. Mol. Psychiatry 2004;9:73. [↩]
8. Gursoy et al. Significance of catecholamine o-methyl transferase gene polymorphism in fibromyalgia syndrome. Rheumatol. Int. 2003;23:104-107. [↩]