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The cause of Fibromyalgia (FM) is not known, but there are many pieces of evidence that point to a fundamental problem in the way the spinal cord and brain are processing pain signals. Simplistically, it is as if the "volume control" in the nerves throughout the body is turned up too high. Possible triggers of FM include infections, physical trauma, psychological stress, hormonal alterations (e.g., hypothyroidism), drugs, vaccines and certain catastrophic events (such as war).

Using brain scans on patients with fibromyalgia, researchers have discovered an abnormal increase in blood flow (called "brain perfusion") in an area of the brain that discriminates the intensity of pain, and a decrease in blood flow in areas thought to be involved in the emotional response to pain. These abnormalities were unrelated to the patients' depression and anxiety levels, reinforcing the idea that fibromyalgia is a real disorder, rather than a result of depression.

Patients with fibromyalgia seem to be more sensitive to sounds than those without the condition. This increased sensitivity may be due to an abnormality in sensory processing by the central nervous system.

Biologic Variables

Certain biologic variables contribute to the development and persistence of FM, although none, as a single element, explains all facets of FM. Certain variables (eg, physical trauma, exposure to toxins) have been widely incriminated by the public but are actually of little significance in the etiology of FM as shown by recent prospective research studies.

1. Inheritance

Family studies initially pointed to a role for genes in FM. With application of sophisticated genotyping and statistical methodology, the extremely important genetic contribution to FM and related central sensitivity syndromes is becoming increasingly recognized. For example, altered serotonin metabolism in a subgroup of patients with FM has been linked to a genotype of the promoter region of the serotonin transporter gene.

2. Sex

Sex-related effects are important in FM and with pain in general. Central pain modulatory systems in females are influenced by phasic alterations in reproductive hormone levels. Aversive stimuli and stressful tasks are more likely to evoke SNS, HPA axis, and psychologic responses in females than in males.

3. Disturbed Sleep Patterns

  • Alpha-EEG Anomaly
    The alpha-EEG sleep anomaly was first described by Hauri and Hawkins, who used the term alpha-delta sleep to characterize a mixture of alpha and delta waves in a small group of psychiatric patients described as having "a general feeling of chronic somatic malaise and fatigue". Researchers found that most FM patients could fall asleep without much trouble, however, their deep level (or stage 4 sleep) was constantly interrupted by bursts of wide-awake brain activity. This leaves sufferers feeling tired and drained. An alarming percentage of Fibromyalgia sufferers have Alpha EEG Anomaly.

  • Restless Leg Syndrome (RLS)
    Many people with FM suffer from Restless Leg Syndrome (RLS) symptoms. RLS causes unpleasant sensations in the lower limbs, so much so that the limbs have to be moved in order to reduce the pain. RLS occurs mostly at night, between the hours of 10:00 pm and 4:00 am, although it can occur throughout the day in severe cases. It is thought that somewhere between 20% and 40% of FM sufferers also have RLS.
    The sensations are unusual and unlike other common sensations, and those with RLS have a hard time describing them. People use words such as: uncomfortable, antsy, electrical, creeping, painful, itching, pins and needles, pulling, creepy-crawly, ants inside the legs, and many others. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still have a strong urge to move.

  • Bruxism
    Bruxism or teeth grinding, frequently affects people with FM. Bruxism is thought to be a part of a disease that is closely related to FM, called Temporomandibular Joint Disorder (TMJD).

    This disorder causes muscle pain in the face, neck, shoulders, and back, and often leads to grinding of the teeth. 75% of people with FM also have TMJD. Bruxism usually occurs when you are sleeping. For some reason, sufferers begin to clench the muscles in their face causing their teeth to grind together.

    Often, bruxism occurs during sleep; even during short naps. In a typical case, the canines and incisors are commonly moved against each other laterally, i.e. with a side to side action. This abrades tooth enamel, removing the sharp biting surfaces and flattening the edges of the teeth. Sometimes, there is a tendency to grind the molars together, which can be loud enough to wake a sleeping partner. Some will clench without significant side to side jaw movement. Bruxism is one of the most common sleep disorders.

    Almost all patients with FM sleep poorly, hence the common report that a night of poor sleep is followed by a more painful day. Eighty Nine percent of FM patients we surveyed report serious problems sleeping. Indeed, intrusion of alpha waves into slow delta wave stage III/IV (deep) sleep was the first objective abnormality observed in FM. Although not the proximate cause of FM, abnormal sleep affects both limbs of the stress response system and contributes to negative mood and cognitive difficulties.

4. Trauma and Tissue Injury

Trauma such as a car accident, a slip and fall, and any other physical trauma to the body has been named a possible cause of FM. It's interesting that 57% of those responding to our FM/CFS/ME Survey have stated that they began having the symptoms of FM after a whiplash or major injury from an accident, whether a car accident or otherwise.

The preponderance of current evidence does not support physical trauma as a significant causative factor in the development of FM. At a clinical level, however, patients who attribute their FM to trauma have more perceived disability, self-reported pain, life interference, and affective distress than patients with idiopathic onset.

5. Stress/Neuroendocrine and Autonomic Dysregulation

A large body of data suggests that FM, chronic fatigue syndrome, regional chronic pain syndromes, and certain emotional disorders that frequently coexist with FM all involve central dysregulation of the stress response system. Here, various forms of stress function as initiators or perpetuators of functional alterations in the corticotropin-releasing hormone (CRH) neuron, with associated effects on the HPA axis, other neuroendocrine axes, and the SNS.

Subtle abnormalities in the stress response system, which cannot be detected by routine clinical and laboratory assessments, may contribute to the diverse clinical manifestations in this spectrum of illnesses. Although incomplete, the emerging evidence is beginning to clarify how the brain, endocrine, and immune systems (especially proinflammatory cytokines) interact in the pathophysiology of pain, fatigue, neurally mediated hypotension, depression, anxiety, and poor sleep.

The extremely high prevalence of stress-related disorders in society may reflect maladaptation of the stress response system in the face of the almost universal stress and consequent distress that characterizes modern life.

Central sensitization and abnormal central nociceptive processing: FM pain can now be classified as a neurosensory disorder.

Viruses or other infections: While considered unlikely to be sole triggers, infection may contribute to exacerbation of symptomatology via cytokine-vagus nerve stimulation of the CRH neuron/stress response system in bidirectional brain–immune system communication.

Decreased collagen cross-linking, hypermobility, Chiari malformation, and environmental chemicals: The relationship of these variables to the development of FM is unclear.

Researchers have found elevated levels of spinal fluid substance P, a pain amplifier; lower levels of serotonin, and low production of cortisol (a stress hormone). A recent MRI study of the brain conducted by Dr. Patrick Wood of Louisiana State University Medical Center in Shreveport, LA, has revealed a possible root cause of FM is a lack of dopamine (a brain chemical) in the brain.

His studies revealed that FM patients had significantly lower dopamine levels. In his drug study, patients were given medication to increase dopamine levels (medicines usually given to Parkinson Disease patients). Patients using this medication reported significant improvement of pain and other symptoms of FM. Is this dopamine theory really a theory, or is it fact? No one will really say with 100% certainty. More research is definitely needed.

Fibromyalgia may be linked to physical or emotional trauma via post-traumatic stress disorder.

Cognitive-Behavioral Variables

Pain catastrophizing, defined as characterizing pain as unbearable or horrible, is an important factor in the experience of pain. Recent research using functional magnetic resonance imaging (fMRI) to measure regional cerebral blood flow (rCBF) and quantitative sensory testing (QST) techniques has demonstrated that pain perception is augmented by increased activity in response to painful stimuli in brain areas involved in anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal anterior cingulate gyrus, dorsolateral prefrontal cortex), and emotional aspects of pain (claustrum, closely connected to the amygdala) in persons with high catastrophizing.

1. Depression and Anxiety

Lifetime psychiatric comorbidity is common in individuals with FM, including mood disorders (bipolar disorder, major depressive disorder), anxiety disorders (generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, PTSD, social phobia), eating disorders, and substance use disorders. Patients with FM can be subgrouped based on pressure-pain thresholds (degree of tenderness with application of pressure) and such psychological factors. Low tenderness is associated with moderate depression/anxiety, moderate catastrophizing, and moderate control over pain; high tenderness is associated with high depression/anxiety, high catastrophizing, and low control over pain; extremely high tenderness is associated with normal levels of depression/anxiety, very low catastrophizing, and highest control over pain.

Depression contributes to the subjective unpleasantness and distress of pain through parallel, somewhat independent neural pain processing networks for purely sensory and affective pain elements. This has been demonstrated in studies combining QST and fMRI in healthy subjects, subjects with FM and no depression, and subjects with FM and comorbid depression. The first two groups exhibit increased rCBF only in the somatosensory cortices and the anterior insula; the group with FM and depression shows, in addition, increased rCBF in the amygdala and contralateral anterior insula, which are involved in affective pain processing.

However, chronic pain is not simply a manifestation of depression. Despite common reports of pain and other somatic symptoms, patients with pure major depression actually have fewer tender points than patients with FM, increased pain thresholds, and more stoical responses to pain stimuli.

2. Personality Traits and Disorders

Personality traits have the largest effect on the cognitive processes by which people attach meanings and implications to their pain. For example, neuroticism, which is associated with hypochondriasis, irritability, and emotional disturbance, has no influence on the discrimination of thermal pain but exerts powerful influences in the delayed reflective stage of pain (ie, at the level of emotions related to suffering, including depression, anxiety, and, especially, frustration).

Several personality styles among patients with FM are encountered in clinical practice. Most common is a perfectionism-compulsiveness personality, characterized by a rigid belief system in the need to be perfect, high underlying anxiety, and an unawareness of feelings and emotions. Another common personality style is the self-sacrificing type, characterized by a tendency to put everyone else's needs before their own. Less common is the "wounded warrior" type, who may be totally helpless and disabled physically and psychologically, carrying a great burden of adverse psychosocial experiences and psychiatric comorbidity. Theses three personality styles are difficult to treat and often require counseling or psychiatric intervention. The "resilient" patient who lacks maladaptive schemas and psychiatric comorbidity has a much better prognosis.

3. Environmental and Sociocultural Variables

Multiple experiences and forces in a person's environment and social culture influence the pain experience, either positively (eg, job satisfaction in a person who strains his or her back at work) or negatively (eg, physician who medicalizes a minor injury by diagnostic waffling and inappropriate diagnostic testing). Environmental and sociocultural variables include:

Psychosocial experiences during childhood (eg, school stress, role models, unhappy families, abuse) that shape the cognitive, affective, and behavioral aspects of pain in adults.

Some studies show that two thirds of patients with chronic pain have first-degree relatives with chronic pain, one third have a family member with an affective illness, and one third have a family member with alcohol abuse. In our survey, 24% of those surveyed grew up with an alcoholic parent, where 20% grew up with a chronically ill parent.

Childhood physical, emotional, or sexual abuse appears to be a common antecedent of anxiety, somatization, and chronic pain in many adults. For example, in a community population-based screening survey, the association of childhood abuse and the presence of more than 5 tender points (a characteristic of FM) in adults was very strong (OR, 6.9; 95% CI, 2.0-24.6). Biologic vulnerability likely derives, in part, from persisting effects of early life stresses on the stress response system.

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