Fibromyalgia Booklet

8/14/2019 Fibromyalgia Booklet

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Fibromyalgia

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Fibromyalgia

Classification and externalresources

ICD-10 M79.7

ICD-9 729.1

MedlinePlus 000427

eMedicine med/790

med/2934

ped/777pmr/47

MeSH D005356

Fibromyalgia (FM) is a disorder classified by the presence of chronic widespreadpainand tactile allodynia.[1] While the criteriafor such an entity have not yet been thoroughly

developed, the recognition that fibromyalgia involves more than just pain has led to the

frequent use of the term "fibromyalgiasyndrome". It is notcontagious, and recent studiessuggest that people with fibromyalgia may be genetically predisposed.[2]The disorder is

not directly life-threatening. The degree of symptoms may vary greatly from day to day

with periods of flares (severe worsening of symptoms) or remission; however, thedisorder is generally perceived asnon-progressive.[3]

Contents

[hide]

1 History 2 Incidence

3 Symptoms

o 3.1 Variability of symptoms

4 Proposed causes and pathophysiology

o 4.1 Genetics

o 4.2 Stress

o 4.3 Dopamine abnormality
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o 4.4 Serotonin

o 4.5 Sleep disturbance

o 4.6 Human growth hormone

o 4.7 Deposition disease

o 4.8 Other hypotheses

o 4.9 Always a comorbid disease? 5 Diagnosis

o 5.1 Differentials

6 Treatment

o 6.1 Medications

6.1.1 Pain relief

6.1.2 Muscle relaxants

6.1.3 Tricyclic antidepressants (TCAs)

6.1.4 Selective serotonin reuptake inhibitors (SSRIs)

6.1.5 Anti-seizure drugs

6.1.6 Dopamine agonists

6.1.7 Combination therapy 6.1.8 Central Nervous System (CNS) Stimulants

6.1.9 Cannabis and cannabinoids

o 6.2 Topical remedies

o 6.3 Non-drug treatment

6.3.1 Physical treatments

6.3.2 Psychological/behavioral therapies

6.3.3 Dietary treatment

o 6.4 Investigational treatments

7 Living with fibromyalgia

8 Controversies

9 References 10 Further reading

11 See also

12 External links

[edit] History

Fibromyalgia has been studied since the early 1800s and referred to by a variety offormer names, including muscular rheumatism and fibrositis.[4] The termfibromyalgia

was coined in 1976 to more accurately describe the symptoms, from the Latinfibra(fiber)[5] and the Greekwords myo (muscle)[6] and algos (pain).[7]

In 1981, Dr. Muhammad B. Yunus published the "first controlled study of the clinicalcharacteristics" of the fibromyalgia syndrome, for which he is considered "the father of

our modern view of fibromyalgia."[8][9] His work was the "first controlledclinical study"

of fibromyalgia with validation of known symptomsand tender points, and he alsoproposed "the first data-based criteria." In 1984, he proposed the important concept that
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the fibromyalgia syndrome and other similar conditions are interconnected. In 1986, he

showed serotonergic and norepinephric drugs to be effective.[10]

Yunus later emphasized a "biopsychosocial perspective" of fibromyalgia, which is

considered the "only way to synthesize the disparate contributions of such variables as

genes and adverse childhood experiences, life stress and distress, posttraumatic stressdisorder, mood disorders, self-efficacy for pain control, catastrophizing, coping style, andsocial support into the evolving picture of central nervous system dysfunction vis-a-vis

chronic pain and fatigue."[8][9]

Fibromyalgia was recognized by the American Medical Association as an illness and acause of disability in 1987.[citation needed] In an article the same year, in the Journal of the

American Medical Association, a physician named Dr. Don Goldenberg also called the

disorder fibromyalgia.[citation needed] The ACR published a criteria for fibromyalgia in 1990,

and developed neurohormonal mechanisms with central sensitizationin the 1990s.[10]

[edit] Incidence

It affects more females than males, with a ratio of 9:1 by American College of

Rheumatology (ACR) criteria.[11] Fibromyalgia is seen in about 2% of the general

population.[12] It is most commonly diagnosed in individuals between the ages of 20 and50, though onset can occur in childhood.

[edit] Symptoms

The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to

light touch. There is also typically moderate to severe fatigue. Those affected may alsoexperience heightenedsensitivity of the skin (also calledallodynia), 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 offibromyalgia. Indeed, studies suggest that sleep disturbances are related to a phenomenon

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.

An example of tactile allodynia is when a person perceives light pressure or the

movement of clothes over the skin as painful, whereas a healthy individual would not feel

pain. Fibromyalgia patients are often affected by a number of symptoms other than pain,including debilitating fatigue, abnormal sleep architecture, [13] (meaning the brain does

not reach all the restorative levels of sleep necessary for overall health), functional bowel

disturbances,[14] and a variety of neuropsychiatric problems including cognitivedysfunction, [15]which can mean short and/or long term memory problems, slowed

information processing ability, diminished attention span and anxiety and depressive

symptoms.[16]
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In addition, many patients experience cognitive dysfunction (known as "brain fog" or

"fibrofog"), which may be characterized by impaired concentration and short-termmemory consolidation, impaired speed of performance, inability to multi-task, and

cognitive overload.[17][18] Many experts suspect that "brain fog" is directly related to the

sleep disturbances experienced by sufferers of fibromyalgia.[citation needed]

Other symptoms often attributed to fibromyalgia that may possibly be due to acomorbiddisorder include myofascial pain syndrome, diffuse non-dermatomalparesthesias,

functional bowel disturbances and irritable bowel syndrome (possibly linked to lower

levels ofghrelin[2], genitourinary symptoms and interstitial cystitis), dermatologicaldisorders, headaches,myoclonic twitches, and symptomatic hypoglycemia. Although

fibromyalgia is classified based on the presence of chronic widespread pain, pain may

also be localized in areas such as theshoulders,neck, lowback, hips, or other areas.Many sufferers also experience varying degrees of facial pain and have high rates of

comorbid temporomandibular joint disorder. Not all patients have all symptoms.

Symptoms can have a slow onset, and many patients have mild symptoms beginning inchildhood, that are often misdiagnosed as growing pains.[citation needed] Symptoms are oftenaggravated by unrelated illness or changes in the weather. [citation needed]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 fromperforming normal activities such as driving a car or walking up stairs. The disorder does

not cause inflammation as is characteristic ofrheumatoid arthritis, although some

NSAIDs may temporarily reduce pain symptoms in some patients. Their use, however, is

limited, and often of little to no value in pain management.[19]

[edit] Variability of symptoms

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

Increasedpsychosocialstress Meador, MD, Clifton K. (May 2008).Puzzling

Symptoms. Cable Publishing. ISBN 13:978-1-934980-11-8.

Excessive physical exertion (exercise seems to decrease the pain threshold of

people with fibromyalgia but increase it in healthy individuals) [20]

Lack ofslow-wave sleep

Changes in humidity and barometric pressure[citation needed]

[edit] Proposed causes and pathophysiology

The cause of fibromyalgia is unknown. Fibromyalgia can, but does not always, start as aresult of some traumasuch as a traffic accident, major surgery, or disease. Some evidence

shows that Lyme Disease may be a trigger of fibromyalgia symptoms.[21] Another study

suggests that more than one clinical entity may be involved, ranging from a mild,

idiopathic inflammatoryprocess toclinical depression[22]
http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-pmid17041327-16#cite_note-pmid17041327-16http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-17#cite_note-17http://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Comorbidityhttp://en.wikipedia.org/wiki/Comorbidityhttp://en.wikipedia.org/wiki/Myofascial_pain_syndromehttp://en.wikipedia.org/wiki/Myofascial_pain_syndromehttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Irritable_bowel_syndromehttp://en.wikipedia.org/wiki/Ghrelinhttp://www.ncbi.nlm.nih.gov/pubmed/17689128?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://en.wikipedia.org/wiki/Urinary_systemhttp://en.wikipedia.org/wiki/Interstitial_cystitishttp://en.wikipedia.org/wiki/Dermatologyhttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Myoclonushttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Shoulderhttp://en.wikipedia.org/wiki/Shoulderhttp://en.wikipedia.org/wiki/Neckhttp://en.wikipedia.org/wiki/Neckhttp://en.wikipedia.org/wiki/Neckhttp://en.wikipedia.org/wiki/Backhttp://en.wikipedia.org/wiki/Hiphttp://en.wikipedia.org/wiki/Temporomandibular_joint_disorderhttp://en.wikipedia.org/wiki/Growing_painshttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Rheumatoid_arthritishttp://en.wikipedia.org/wiki/Rheumatoid_arthritishttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-Yahoo_health-18#cite_note-Yahoo_health-18http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-Yahoo_health-18#cite_note-Yahoo_health-18http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=4http://en.wikipedia.org/wiki/Psychosocialhttp://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/w/index.php?title=Puzzling_Symptoms&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Puzzling_Symptoms&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Puzzling_Symptoms&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Cable_Publishing&action=edit&redlink=1http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-19#cite_note-19http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-19#cite_note-19http://en.wikipedia.org/wiki/Slow-wave_sleephttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=5http://en.wikipedia.org/wiki/Physical_traumahttp://en.wikipedia.org/wiki/Physical_traumahttp://en.wikipedia.org/wiki/Lyme_Diseasehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-20#cite_note-20http://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-21#cite_note-21http://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-pmid17041327-16#cite_note-pmid17041327-16http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-17#cite_note-17http://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Comorbidityhttp://en.wikipedia.org/wiki/Myofascial_pain_syndromehttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Irritable_bowel_syndromehttp://en.wikipedia.org/wiki/Ghrelinhttp://www.ncbi.nlm.nih.gov/pubmed/17689128?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://en.wikipedia.org/wiki/Urinary_systemhttp://en.wikipedia.org/wiki/Interstitial_cystitishttp://en.wikipedia.org/wiki/Dermatologyhttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Myoclonushttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Shoulderhttp://en.wikipedia.org/wiki/Neckhttp://en.wikipedia.org/wiki/Backhttp://en.wikipedia.org/wiki/Hiphttp://en.wikipedia.org/wiki/Temporomandibular_joint_disorderhttp://en.wikipedia.org/wiki/Growing_painshttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Rheumatoid_arthritishttp://en.wikipedia.org/wiki/NSAIDhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-Yahoo_health-18#cite_note-Yahoo_health-18http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=4http://en.wikipedia.org/wiki/Psychosocialhttp://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/w/index.php?title=Puzzling_Symptoms&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Puzzling_Symptoms&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Cable_Publishing&action=edit&redlink=1http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-19#cite_note-19http://en.wikipedia.org/wiki/Slow-wave_sleephttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=5http://en.wikipedia.org/wiki/Physical_traumahttp://en.wikipedia.org/wiki/Lyme_Diseasehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-20#cite_note-20http://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Clinical_depressionhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-21#cite_note-21


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[edit] Genetics

By using self-reported "Chronic Widespread Pain" (CWP) as a surrogate marker for

fibromyalgia, the Swedish Twin Registryfound that a modest genetic contribution mayexist:[23][24]

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

Dizygotic twinswith CWP have a 7% chance that their twin sibling has CWP

[edit] Stress

Studies have shown that stress is a significant precipitating factor in the development of

fibromyalgia,[25] and that PTSDis linked with fibromyalgia.[26][27] The Amital study found

that 49% of PTSD patients fulfilled the criteria for FMS, compared with none of thecontrols.

A non-mainstream hypothesis that fibromyalgia may be apsychosomatic illness has beendescribed by John E. Sarno's "tension myositis syndrome". He believes many cases of

chronic pain result from changes in the body caused by the mind's subconscious strategyof distracting painful or dangerous emotions. Education, attitude change, and, in some

cases, psychotherapy are treatments proposed to stop the brain from using that

strategy.[28][29][30][31]

[edit] Dopamine abnormality

Dopamine is acatecholamineneurotransmitterperhaps best known for its role in the

pathology ofschizophrenia, Parkinson's diseaseandaddiction. There is also strong

evidence for a role of dopamine in restless leg syndrome[32], which is a common co-morbid condition in patients with fibromyalgia. [33] In addition, dopamine plays a critical

role in pain perception and natural analgesia. Accordingly, musculoskeletal paincomplaints are common among patients with Parkinson's disease [34], which is

characterized by drastic reductions in dopamine owing to neurodegeneration of

dopamine-producing neurons, while patients with schizophrenia, which is thought to bedue (in part) to hyperactivity of dopamine-producing neurons, have been shown to be

relatively insensitive to pain.[35][36] Interestingly, patients with restless legs syndrome have

also been demonstrated to havehyperalgesiato static mechanical stimulation.[37]

Fibromyalgia has been commonly referred to as a "stress-related disorder" due to its

frequent onset and worsening of symptoms in the context of stressful events.[38][39] It wastherefore proposed that fibromyalgia may represent a condition characterized by low

levels of central dopamine that likely results from a combination of genetic factors andexposure to environmental stressors, including psychosocial distress, physical trauma,

systemic viral infections or inflammatory disorders (e.g. rheumatoid arthritis, systemic

lupus erythematosus).[40] This conclusion was based on three key observations: (1)

fibromyalgia is associated with stress; (2) chronic exposure to stress results in adisruption of dopamine-related neurotransmission[41]; and (3) dopamine plays a critical
http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=6http://www.meb.ki.se/twinreg/index_en.htmlhttp://www.meb.ki.se/twinreg/index_en.htmlhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-PMID16646040-22#cite_note-PMID16646040-22http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-PMID16908799-23#cite_note-PMID16908799-23http://en.wikipedia.org/wiki/Monozygotic_twinshttp://en.wikipedia.org/wiki/Twinshttp://en.wikipedia.org/wiki/Twinshttp://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=7http://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-24#cite_note-24http://en.wikipedia.org/wiki/PTSDhttp://en.wikipedia.org/wiki/PTSDhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-25#cite_note-25http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-25#cite_note-25http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-26#cite_note-26http://en.wikipedia.org/wiki/Psychosomatic_illnesshttp://en.wikipedia.org/wiki/Psychosomatic_illnesshttp://en.wikipedia.org/wiki/John_E._Sarnohttp://en.wikipedia.org/wiki/Tension_myositis_syndromehttp://en.wikipedia.org/wiki/Chronic_painhttp://en.wikipedia.org/wiki/Subconscioushttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-27#cite_note-27http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-28#cite_note-28http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-29#cite_note-29http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-20-20-30#cite_note-20-20-30http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=8http://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Parkinson's_diseasehttp://en.wikipedia.org/wiki/Parkinson's_diseasehttp://en.wikipedia.org/wiki/Addictionhttp://en.wikipedia.org/wiki/Addictionhttp://en.wikipedia.org/wiki/Restless_leg_syndromehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-31#cite_note-31http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-31#cite_note-31http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-31#cite_note-31http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-32#cite_note-32http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-33#cite_note-33http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-34#cite_note-34http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-34#cite_note-34http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-35#cite_note-35http://en.wikipedia.org/wiki/Hyperalgesiahttp://en.wikipedia.org/wiki/Hyperalgesiahttp://en.wikipedia.org/wiki/Hyperalgesiahttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-36#cite_note-36http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-36#cite_note-36http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-37#cite_note-37http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-38#cite_note-38http://en.wikipedia.org/wiki/Rheumatoid_arthritishttp://en.wikipedia.org/wiki/Lupus_erythematosushttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-39#cite_note-39http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-40#cite_note-40http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-40#cite_note-40http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=6http://www.meb.ki.se/twinreg/index_en.htmlhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-PMID16646040-22#cite_note-PMID16646040-22http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-PMID16908799-23#cite_note-PMID16908799-23http://en.wikipedia.org/wiki/Monozygotic_twinshttp://en.wikipedia.org/wiki/Twinshttp://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=7http://en.wikipedia.org/wiki/Stress_(medicine)http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-24#cite_note-24http://en.wikipedia.org/wiki/PTSDhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-25#cite_note-25http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-26#cite_note-26http://en.wikipedia.org/wiki/Psychosomatic_illnesshttp://en.wikipedia.org/wiki/John_E._Sarnohttp://en.wikipedia.org/wiki/Tension_myositis_syndromehttp://en.wikipedia.org/wiki/Chronic_painhttp://en.wikipedia.org/wiki/Subconscioushttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-27#cite_note-27http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-28#cite_note-28http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-29#cite_note-29http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-20-20-30#cite_note-20-20-30http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=8http://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Schizophreniahttp://en.wikipedia.org/wiki/Parkinson's_diseasehttp://en.wikipedia.org/wiki/Addictionhttp://en.wikipedia.org/wiki/Restless_leg_syndromehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-31#cite_note-31http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-32#cite_note-32http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-33#cite_note-33http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-34#cite_note-34http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-35#cite_note-35http://en.wikipedia.org/wiki/Hyperalgesiahttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-36#cite_note-36http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-37#cite_note-37http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-38#cite_note-38http://en.wikipedia.org/wiki/Rheumatoid_arthritishttp://en.wikipedia.org/wiki/Lupus_erythematosushttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-39#cite_note-39http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-40#cite_note-40


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role in modulating pain perception and central analgesia in such areas as thebasal

ganglia[42] including the nucleus accumbens[43] ,insular cortex[44] , anterior cingulatecortex[45] ,thalamus[46] ,periaqueductal gray[47] , andspinal cord[48] [49].

In support of the 'dopamine hypothesis of fibromyalgia', a reduction in dopamine

synthesis has been reported by a study that usedpositron emission tomography (PET) anddemonstrated a reduction in dopamine synthesis among fibromyalgia patients in severalbrain regions in which dopamine plays a role in inhibiting pain perception, including the

mesencephalon, thalamus, insular cortex and anterior cingulate cortex.[50] A subsequent

PET study demonstrated that, whereas healthy individuals release dopamine into thecaudate nucleusandputamen during a tonic experimental pain stimulus (i.e. hypertonic

saline infusion into a muscle bed)[51], fibromyalgia patients fail to release dopamine in

response to pain and, in some cases, actually have a reduction in dopamine levels duringpainful stimulation. [52] Moreover, a substantial subset of fibromyalgia patients respond

well in controlled trials topramipexole, a dopamine agonistthat selectively stimulates

dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless legs

syndrome.

[53]

Trials of other dopamine agonists are currently ongoing.

[edit] Serotonin

Serotonin is a neurotransmitterthat is known to play a role in regulating sleep patterns,

mood, feelings of well-being, concentration and descending inhibition of pain.

Accordingly, it has been hypothesized that thepathophysiology underlying the symptoms

of fibromyalgia may be a dysregulation of serotonin metabolism, which may explain (inpart) many of the symptoms associated with the disorder. Thishypothesis is derived in

part by the observation of decreased serotonin metabolites in patientplasma[54]and

cerebrospinal fluid.[55] However,selective serotonin reuptake inhibitors (SSRIs) have met

with limited success in alleviating the symptoms of the disorder, while drugs with activityas mixed serotonin-norepinephrine reuptake inhibitors (SNRIs) have been more

successful[56]. Accordingly,duloxetine (Cymbalta), a SNRI originally used to treatdepression and painful diabetic neuropathy, has been demonstrated by controlled trials to

relieve symptoms of some patients. Eli Lilly and Company, the manufacturer of

duloxetine has submitted a supplementary new drug application (sNDA) to the FDA for

approval of it use in the treatment of FM. The relevance of dysregulated serotoninmetabolism to the pathophysiology is a matter of debate.[57] Ironically, one of the more

effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3

antagonists) actually block some of the effects of serotonin.[58]

[edit] Sleep disturbance

Electroencephalography studies have shown that people with fibromyalgia lackslow-

wave sleep and circumstances that interfere with stage four sleep (pain, depression,serotonin deficiency, certain medications oranxiety) may cause or worsen the

condition.[59] According to the sleep disturbance hypothesis, an event such as a trauma or

illness causes sleep disturbance and possibly initial chronic pain that may initiate thedisorder. The hypothesis supposes that stage 4 sleep is critical to the function of the
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myalgia#cite_note-45#cite_note-45http://en.wikipedia.org/wiki/Periaqueductal_grayhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-46#cite_note-46http://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-47#cite_note-47http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-48#cite_note-48http://en.wikipedia.org/wiki/Hypothesishttp://en.wikipedia.org/wiki/Positron_emission_tomographyhttp://en.wikipedia.org/wiki/Mesencephalonhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-49#cite_note-49http://en.wikipedia.org/wiki/Caudate_nucleushttp://en.wikipedia.org/wiki/Putamenhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-50#cite_note-50http://en.wikipedia.org/wiki/Fibromyalgia#cite_note-51#cite_note-51http://en.wikipedia.org/wiki/Pramipexolehttp://en.wikipedia.org/wiki/Dopamine_agonisthttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-52#cite_note-52http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=9http://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Pathophysiologyhttp://en.wikipedia.org/wiki/Hypothesishttp://en.wikipedia.org/wiki/Plasmahttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-53#cite_note-53http://en.wikipedia.org/wiki/Cerebrospinal_fluidhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-54#cite_note-54http://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorshttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-55#cite_note-55http://en.wikipedia.org/wiki/Duloxetinehttp://en.wikipedia.org/wiki/Cymbaltahttp://en.wikipedia.org/wiki/Diabetic_neuropathyhttp://en.wikipedia.org/wiki/FDAhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-56#cite_note-56http://en.wikipedia.org/wiki/5-HT3_antagonisthttp://en.wikipedia.org/wiki/5-HT3_antagonisthttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-57#cite_note-57http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=10http://en.wikipedia.org/wiki/Electroencephalographyhttp://en.wikipedia.org/wiki/Slow-wave_sleephttp://en.wikipedia.org/wiki/Slow-wave_sleephttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-58#cite_note-58


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nervous system, as it is during that stage that certain neurochemical processes in the body

'reset'. In particular, pain causes the release of the neuropeptidesubstance P in the spinalcord which has the effect of amplifying pain and causing nerves near the initiating ones to

become more sensitive to pain. Under normal circumstances, areas around a wound to

become more sensitive to pain but if pain becomes chronic and body-wide this process

can run out of control. The sleep disturbance hypothesis holds that deep sleep is critical toreset the substance P mechanism and prevent this out-of-control effect.

The sleep disturbance/substance P hypothesis could explain "tender points" that are

characteristic of fibromyalgia but which are otherwise enigmatic, since their positionsdon't correspond to any particular set of nerve junctions or other obvious body

structures.[citation needed] The hypothesis proposes that these locations are more sensitive

because the sensory nerves that serve them are positioned in the spinal cord to be moststrongly affected by substance P. This hypothesis could also explain some of more

general neurological features of fibromyalgia, since substance P is active in many other

areas of the nervous system. The sleep disturbance hypothesis could also provide a

possible connection between fibromyalgia, chronic fatigue syndrome (CFS) andpost-polio syndrome through 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 producesome neuropeptides, and thus injury or imbalance in this area could cause both CFS and

sleep-related fibromyalgia.

Critics of the hypothesis argue that it does not explain slow-onset fibromyalgia,

fibromyalgia present without tender points, or patients without heightened painsymptoms, and a number of the non-pain symptoms present in the disorder.[citation needed]

[edit] Human growth hormone

An alternate hypothesis suggests that stress-induced problems in the hypothalamus may

lead to reduced sleep and reduced production ofhuman growth hormone (HGH) during

slow-wave sleep. People with fibromyalgia tend to produce inadequate levels of HGH.Most patients with FM with low IGF-I levels failed to secrete HGH after stimulation with

clonidine and l-dopa.[citation needed]

This view is supported by the fact that those hormones under the direct or indirect control

of HGH, including IGF-1, cortisol, leptin andneuropeptide Yare abnormal in peoplewith fibromyalgia,[60] In addition, treatment with exogenous HGH or growth hormone

secretagogue reduces fibromyalgia related pain and restores slow wave sleep

[61][62][63][64]

though there is disagreement about the proposition.[65]

[edit] Deposition disease

The 'deposition hypothesis of fibromyaglia' posits fibromyalgia is due to intracellular

phosphate and calcium accumulations that eventually reaches levels sufficient to impedethe ATP process, possibly caused by a kidney defect or missing enzyme that prevents the
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removal of excess phosphates from the blood stream. Accordingly, proponents of this

hypothesis suggest that fibromyalgia may be an inherited disorder, and that phosphatebuild-up in cells is gradual but can be accelerated by trauma or illness. Calcium is

required for the excess phosphate to enter the cells.[citation needed]The additional phosphate

slows down the ATP process; however the excess calcium prods the cell to continue

producing ATP.[66]

Diagnosis is made with a specialized technique called mapping, a gentle palpitation of the

muscles to detect lumps and areas of spasm thought to be caused by an excess ofcalcium

in the cytosol of the cells. The mapping technique is notably different from the manualtenderpoint examination[67] upon which a diagnosis of fibromyalgia depends and is

purportedly different from the detection oftrigger points that characterize the myofascial

pain syndrome.[citation needed]

While this hypothesis does not identify the causative mechanism in the kidneys, itproposes a treatment known as guaifenesin therapy. This treatment involves

administering the drug guaifenesin to a patient's individual dosage, avoiding salicylicacid in medications or on the skin. Often products forsalicylate sensitivityare veryhelpful. If the patient is also hypoglycemic, a diet is designed to keepinsulinlevels low.

The phosphate build-up hypothesis explains many of the symptoms present in

fibromyalgia.[citation needed]and proposes an underlying cause. The guaifenesin treatment,

based on this hypothesis, has received mixed reviews, with some practitioners claimingmany near-universal successes[citation needed] and others reporting no success. Of note,

guaifenesin is also a central acting muscle relaxant used in veterinary anaesthesia[68] that

is structurally related to methocarbamol, a property that might explain its utility in somefibromyalgia patients. A controlled trial of guaifenesin for the treatment of fibromyalgia

demonstrated no evidence for efficacy of this medication.

[69]

However, this study hasbeen criticized by the chief proponent of the deposition hypothesis for not limitingsalicylic acid exposure in patients, and for studying the effectiveness of only guaifenesin,

not the entire treatment method.[70]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 hypothesis. It should be noted that nothinginthe scientific literature supports the proposition that fibromyalgia patients have excessive

levels of phosphate in their tissues.

[edit] Other hypotheses

Other hypotheses have been proposed related to various toxins from the patient'senvironment, viral causes such as theEpstein-Barr Virus, growth hormonedeficienciespossibly related to an underlying (maybe autoimmune) disease affecting the

hypothalamus gland, an aberrant immune response to intestinal bacteria,[71][72]

neurotransmitterdisruptions in the central nervous system, and erosion of the protectivechemical 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.[73][74] This association has
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not repeated in a number of related studies,[75] and the US-FDA concluded "the weight of

the epidemiological evidence published in the literature does not support an associationbetween fibromyalgia and breast implants."[76] Due to the multi-systemic nature of

illnesses such as fibromyalgia and chronic fatigue syndrome (CFS/ME), an emerging

branch of medical science calledpsychoneuroimmunology(PNI) is looking into how the

various hypotheses fit together.

Another hypothesis on the cause of symptoms in fibromyalgia states that patients suffer

from vasomotordysregulation causing impropervascularflow and hypoperfusion

(decreased blood flow to a given tissue or organ).[77]

[edit] Always a comorbid disease?

Cutting across several of the above hypotheses is the proposition that fibromyalgia isalmost always a comorbid disorder, occurring in combination with some other disorder

that likely served to "trigger" the fibromyalgia in the first place. Two possible triggers are

gluten sensitivityand/or irritable bowel. Irritable bowel is found at high frequency infibromyalgia,[78] and a large coeliac support group survey of adult celiacs revealed that

7% had fibromyalgia and also has a co-occurrence with chronic fatique.[79]

According to this hypothesis, some other disorder (or trauma) occurs first, and

fibromyalgia follows as a result. In some cases, the original disorder abates on its own oris 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.

[edit] Diagnosis

There is still debate over what should be considered essential diagnostic criteria. The

most widely accepted set of classification criteria for research purposes were elaborated

in 1990 by the Multicenter Criteria Committee of thethe American College ofRheumatology. 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 monthsaffecting all four

quadrants of the body, i.e., both sides, and above and below the waist.

Tender pointsthere are 18 designated possible tender or trigger points (although

a person with the disorder may feel pain in other areas as well). During diagnosis,

fourkilograms-force (39 newtons) offorceis exerted at each of the 18 points; thepatient must feel pain at 11 or more of these points for fibromyalgia to beconsidered.[80] Four kilograms of force is about the amount of pressure required to

blanch the thumbnail when applying pressure. This set of criteria was developed

by the American College of Rheumatology as a means of classifying an individualas 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
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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 mayvary with time and circumstance.

[edit] Differentials

A number of other disorders can produce similar symptoms to fibromyalgia:

Chronic fatigue

syndrome

Depression

Ehlers-Danlos

syndrome

Gulf War syndrome

Influenza

Lead poisoning

Lupus erythematosus

Lyme disease

Mercury poisoning

Myofascial pain

syndrome

Tendinitis

Thyroid disease

Vitamin B12

deficiency

Vitamin D deficiency

Whiplash-associated

disorder

Multiple chemical

sensitivity

[edit] Treatment

As with many other syndromes, there is no universally accepted cure for fibromyalgia,

though some physicians claim to have found cures.[81] However, a steady interest in the

disorder on the part of academic researchers as well as pharmaceutical interests has led toimprovements in its treatment, which ranges from symptomatic prescription medication

toalternative andcomplementary medicine.

The European League Against Rheumatism (EULAR) issued the first guidelines[82]for the

treatment of fibromyalgia syndrome (FMS) and published them in the September 17thOn-line First issue of the Annals of the Rheumatic Diseases.

[edit] Medications

Many medications are used to treat specific symptoms of fibromyalgia, such as musclepain and insomnia.

[edit] Pain relief

A number of pain relievers have been prescribed for fibromyalgia. This includesNSAID

medications over the counter, COX-2 inhibitors, and tramadol in prescription form formore advanced cases. Recently,pregabalin (marketed as Lyrica) has been given FDA

approval for the treatment of diagnosed Fibromyalgia.[83]

[edit] Muscle relaxants
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11/23

Muscle relaxants, such ascyclobenzaprine(Flexeril) ortizanidine (Zanaflex), may be

used to treat the muscle pain associated with the disorder.[84][85][86]

[edit] Tricyclic antidepressants (TCAs)

Traditionally, low doses of sedating antidepressants (e.g. amitriptyline and trazodone)have been used to reduce the sleep disturbances that are associated with fibromyalgia and

are believed by some practitioners to alleviate the symptoms of the disorder. Becausedepression 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 orneuropathicpain.[citation needed] It is to be noted that Fibromyalgia is not considered a depressive disorder;

antidepressants are used for their sedating effect to aid in sleep.

[edit] Selective serotonin reuptake inhibitors (SSRIs)

Research data consistently contradict the utility of agents with specificity as serotoninreuptake inhibitors for the treatment of core symptoms of fibromyalgia. [87][88][89]

Moreover, SSRIs are known to aggravate many of the comorbidities that commonly

affect patients with fibromyalgia including restless legs syndrome and sleep

bruxism[90][91][92].

[edit] Anti-seizure drugs

Anti-seizure drugs are also sometimes used, such as gabapentin[93] andpregabalin

(Lyrica). Pregabalin, originally used for the nerve pain suffered by diabetics, has been

approved by the American Food and Drug Administration for treatment of fibromyalgia.

A randomized controlled trial ofpregabalin450 mg/day found that anumber needed totreatof 6 patients for one patient to have 50% reduction in pain.[94]

[edit] Dopamine agonists

Dopamine agonists(e.g.pramipexole (Mirapex) and ropinirole(ReQuip)) have been

studied for use in the treatment of fibromyalgia with good results.[95]A trial oftransdermal rotigotineis currently on going [96].

[edit] Combination therapy

A controlled clinical trial ofamitriptylineand fluoxetinedemonstrated utility when usedin combination.[97]

[edit] Central Nervous System (CNS) Stimulants

Cognitive dysfunction in fibromyalgia, often referred to as brain fog, may be treated

with low doses of central nervous system (CNS) stimulants such as Modafinil, Adderall,

Provigil, Methylphenidate (Ritalin, Ritalin SR, Methylin, Methylin ER.) These non-
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it&section=24http://en.wikipedia.org/wiki/Dopamine_agonistshttp://en.wikipedia.org/wiki/Pramipexolehttp://en.wikipedia.org/wiki/Ropinirolehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-94#cite_note-94http://en.wikipedia.org/wiki/Rotigotinehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-95#cite_note-95http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=25http://en.wikipedia.org/wiki/Amitriptylinehttp://en.wikipedia.org/wiki/Fluoxetinehttp://en.wikipedia.org/wiki/Fibromyalgia#cite_note-pmid8912507-96#cite_note-pmid8912507-96http://en.wikipedia.org/w/index.php?title=Fibromyalgia&action=edit&section=26http://en.wikipedia.org/wiki/Ritalin


12/23

amphetamine stimulants are also used to treat the chronic fatigue that is characteristic of

fibromyalgia.[98][99]

Stimulants may be habit forming and can have other serious side effects, so it is

important to note that other treatments may be effective.[100] Care should be taken with

any prescription, as people with fibromyalgia are known to be sensitive to medications.[101]

[edit] Cannabis and cannabinoids

Fibromyalgia patients frequently self-report using cannabistherapeutically to treat

symptoms of the disorder.[102] Writing in the July 2006 issue of the journal Current

Medical Research and Opinion, investigators at Germany's University of Heidelbergevaluated the analgesic effects of oral THC (9-tetrahydrocannabinol) in nine patients

with fibromyalgia over a 3-month period. Subjects in the trial were administered daily

doses of 2.5 to 15 mg of THC, but received no other pain medication during the trial.

Among those participants who completed the trial, all reported a significant reduction indaily recorded pain and electronically induced pain.[103] Previous clinical and preclinical

trials have shown that both naturally occurring and endogenous cannabinoids hold

analgesic qualities,[104] particularly in the treatment of cancer pain and neuropathicpain,[105][106] both of which are poorly treated by conventional opioids. As a result, some

experts have suggested that cannabinoid agonists would be applicable for the treatment of

chronic pain conditions unresponsive to opioid analgesics such as fibromyalgia, and theypropose that the disorder may be associated with an underlying clinical deficiency of the

endocannabinoid system.[107][108]

[edit] Topical remedies

Users of Epsom Salts in the gel form (Magnesium Sulfate), have reported significant and

lasting relief from pain associated with fibromyalgia. Epsom Salts have long been toutedfor their ability to reduce pain and swelling.[109]

[edit] Non-drug treatment

[edit] Physical treatments

Studies have found exercise improves fitness and sleep and may reduce pain and fatiguein some people with fibromyalgia.[110] Many patients find temporary relief by applying

heat to painful areas. Those with access tophysical therapy,massage, or acupuncturemay find them beneficial.[111] Most patients find exercise, even low intensity exercise tobe extremely helpful.[112]Osteopathic manipulative therapy can also temporarily relieve

pain due to fibromyalgia.[113]

A holistic approachincluding managing diet, sleep, stress, activity, and painis used

by many patients. Dietary supplements, massage, chiropractic care, managing blood
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Documents

Fibromyalgia Booklet