Fibromyalgia

Fibromyalgia comes from “Fibro” for fibrosis, “myo” means muscles and “algia” means pain. Fibromyalgia is a syndrome characterized by widespread pain throughout the body, often associated with fatigue and sleep disorders. It is a disease that does not cause serious complications, but it is very challenging and often prevents the sufferer to perform daily activities.

Prevalence (1)

Statistics show that in industrialized countries, fibromyalgia affects 2% up to 6% of the population.

Fibromyalgia affects about 2–3% of adults, with women affected about three times more often than men. Peak prevalence is between 55 and 64 years old.

Symptoms

The variety and severity of  fibromyalgia symptoms vary from person to person. Chronic pain is the most common symptom. This is usually gradual.

Symptoms may last from several days to several months. People with fibromyalgia have periods of asymptomatic and symptomatic periods. Fatigue and muscle or joint pain are very common, especially after physical or mental stress.

For most people, symptoms of fibromyalgia consist of low tolerance to pain and decreased physical activity. Increasing pain leads the person to be less active. Muscles that are not used for certain periods of time are prone to irritation during activity. People with fibromyalgia are more sensitive to pain and the muscles are more easily irritable. Muscle pain is associated with sleep disturbances and daytime fatigue. Together they lead to decreased activity.

 Causes

Genes Expression

The regulation of the expression of our genes may depend on external factors called epigenetic. The épigénétisme regulates gene activity by facilitating or inhibiting their expression.

This regulation is fundamental because it allows a different reading of a same genetic code. This explains, for example the differences observed between identical twins and may also explain the occurrence of autoimmune diseases and fibromyalgia (2, 3, 4, 5, 6, 7)

Gut flora

The intestinal microflora is a complex community of organisms that colonize the gastrointestinal tract. The composition of the intestinal flora and the number of micro-organisms depend on local environmental conditions.

Gut microbiota has a significant impact on the development of architecture and bowel function. This flora influences the development of gut-associated immune system and influences also the functions of epithelial cells. One of the most important functions of the intestinal “friendly” microflora is to prevent dysbiotic bacteria overgrowth which can generate the inflammatory process leading to the “so-called civilization diseases.“

In addition, the intestinal microbiota plays a crucial role in the development of immunity and has a significant influence on the nutrition and metabolism of the host. However, in genetically predisposed individuals, the gut microbiota is involved in the pathogenesis of many inflammatory diseases (8.9, 10, 11, 49, 50, 51).

Leaky gut

The leaky gut syndrome is a factor that may explain the onset of fibromyalgia. Leaky gut is frequently associated with pathogens overgrowth called dysbiosis responsible for digestive pain and bowel dysfunction. This imbalance in favor of a pathogenic flora is directly correlated to the intensity of the pain encontered in fibromyalgia (12, 13, 14)

This leaky gut syndrome is responsible for an abnormal stimulation of the immune system (80% of our immune system are located in our gut) generating the synthesis of pro-inflammatory compounds.

The restoration of a functional digestive barrier is one of the steps of healing (15, 16).

 Mitochondria and oxidative stress

Fibromyalgia is a form of non-articular  rheumatism (inflammation) characterized by chronic widespread musculoskeletal pain.

Mitochondrial dysfunction causes excessive oxidative stress (17, 18, 19) and a decrease in the synthesis of ATP, the universal energy of our cells explaining one of the symptoms met: fatigue.

Excess oxidative stress is frequently encountered in fibromyalgia (20, 21, 22, 23, 24), the correction of this imbalance is an integral part of the therapeutic treatment (25, 26).

Serotonin : the neurotransmitter of “the zen attitude“

Tryptophan is an essential amino acid that can be metabolized into serotonin, a neurotransmitter of “zen attitude” but in case of inflammation bioavailability of tryptophan to serotonin synthesis is greatly reduced because it is metabolized to substances that play a key role in the modulation of the immune response: the kinurenines.

The Kynurenine pathway has been shown to be involved in many diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, AIDS dementia syndrome, malaria, cancer, depression and schizophrenia (47, 48).

 Hormonal deficiencies

Growth hormone

Although pain is not part of the clinical signs of growth hormone deficiency syndrome, many clinical manifestations are similar. Many studies have shown a decrease in growth hormone secretion in some patients with fibromyalgia. In such patents treatment with growth hormne significantly improves symptoms of fibromyalgia and quality of life suggesting a direct causal link between fibromyalgia and growth hormone deficiency. Despite the use of relatively high doses of growth hormone in such patients, the treatment appears to be well tolerated. Several mechanisms of action have been proposed, including both central pain modulation and periferical musculotendinous effects, as already described in the growth hormone deficiency syndrome (27, 28, 29, 52).

Cortisol

Many studies have shown that the circadian rhythm of cortisol secretion is impaired in patients with fibromyalgia. This abnormal increase in serum cortisol levels at night can be a cause of a symptom frequently encountered : a nonrestorative sleep (30).

The dysfunction of the hypothalamic-pituitary-adrenal with low cortisol values in the morning (31) can cause morning stiffness and pain.The inflammation encountered in fibromyalgia disrupts the activity cortisol receptors reducing its effectiveness on symptoms such as stiffness and pain (32)

Melatonin

Melatonin can improve sleep quality and increase the pain’s threshold (33), it reduces inflammation (34) in patients with fibromyalgia.

Urinary metabolites of melatonin were significantly lower (35), which can have a direct and negative impact on clinical signs that compose the picture of fibromyalgia.

The perception of pain is more pronounced during the day, the high rate of mélatonin during the night produce an analgesic effect.

Melatonin levels are significantly lower in fibromyalgia patients, treatment with melatonin improves pain, fatigue, sleep, morning stiffness and depression (35, 36, 37).

Melatonin has also been found useful in the treatment of irritable bowel syndrome (38) which is involved in fibromyalgia.

Ocytocin

Oxytocin reduces the severity of pain, anxiety and depression and improves the quality of sleep, suggesting that oxytocin may be useful to treat fibromyalgia (39).

Low oxytocin levels are found in depression, in cases of significant pain and stress.

Oxytocin is known to have anti-nociceptive and analgesic effects as well as anxiolytics and antidepressants properties which makes this neuropeptide of great therapeutic value for patients with fibromyalgia (40, 41).

Vitamin D

Vitamin D is an inappropriate name because it is much more an hormone than a vitamin.

Numerous studies have established a link between low levels of 25-hydroxyvitamin D and musculoskeletal pain as experienced in the fibromyalgia syndrome (42, 43, 44, 45).

Prescribing high doses of vitamin D can correct this deficiency and could lead to the resolution of almost all symptoms (46).

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