Fibromyalgia syndrome is a non-articular rheumatic disease that manifests clinically as pain and stiffness in multiple areas of the musculoskeletal system with pressure points in specific areas. Fibromyalgia syndrome can occur secondary to trauma, various rheumatic diseases such as osteoarthritis, rheumatoid arthritis and various non-rheumatic diseases (e.g. hypothyroidism, malignancy). This type of fibromyalgia syndrome is referred to as secondary fibromyalgia syndrome, or primary fibromyalgia syndrome if there are no other disorders.
Causes
The mechanism of the disease is not known. The literature reports that it is related to sleep disorders, abnormal neurotransmitter secretion and immune disorders.
1.Sleep disorders
Sleep disorders affect 60-90% of patients. It is characterized by easy awakening, excessive dreaming, morning mental fatigue, generalized pain and morning stiffness. Nocturnal EEG recordings revealed alpha waves intervening in stage IV delta sleep waves. Interference of non-fast moving eye sleep with a bell can also induce the above EEG patterns and clinical symptoms in volunteers. Other factors affecting sleep, such as stress and environmental noise, can aggravate the symptoms of fibromyalgia syndrome. Therefore, it is speculated that this stage IV sleep abnormality plays an important role in the triggering of fibromyalgia syndrome.
2. Abnormal neurotransmitter secretion
Neurotransmitters such as serotonin and substance P have been reported in the literature to play an important role in the pathogenesis.
The precursor of serotonin is tryptophan, which is absorbed from food protein in the intestine and is mostly bound to plasma protein, with a small portion in a free state. The free tryptophan can be carried by carriers across the blood-brain barrier into brain tissue. 5-HT is then hydroxylated and decarboxylated in 5-HTergic neurons to produce 5-HT. 5-HT released into the synaptic gap is partially reuptaken by presynaptic nerve endings and partially produced by mitochondrial monoamine oxidase to inactive 5-hydroxyindoleacetic acid. 5-HT is also present in the mucosa of the digestive tract, platelets and mammary cells, and because it is difficult to cross the blood-brain barrier, the central nervous system and 5-HT in peripheral blood belongs to two systems. It has been found that.
1. free tryptophan and its transport rate are reduced in the plasma of patients with fibromyalgia syndrome. The degree of reduction correlates with musculoskeletal pain, i.e., the lower the plasma concentration and the rotation ratio, the more pronounced the pain.
2, high affinity 5-HT receptors on platelet membranes, promethazine can bind competitively with 5-HT to platelet receptors, and the 5-HT receptor density on platelet membranes was measured with tritium-labeled promethazine and found to be more affected in fibromyalgia syndrome than in normal subjects.
3, 5-HT was significantly reduced in the brain tissue of presenters with fibromyalgia anterior syndrome than normal subjects. Experiments have shown that 5-HT can regulate non-rapid eye sleep, reduce sensitivity to pain, improve the depressive state, and also enhance the analgesic effect of anesthesia. Amitriptyline and aminophenylcycloheptene can promote the conversion of 5-HT to 5-hydroxyindole acetylase and increase 5-HT concentration, so it is effective in fibromyalgia syndrome. In contrast, administration of the tryptophan hydroxylase inhibitor, p-chlorophenylalanine, results in fibromyalgia syndrome-like pain, which disappears when this drug is discontinued.
Another neurotransmitter associated with fibromyalgia syndrome is substance P. Littlejohn found that physical or chemical stimuli induced a marked cutaneous engorgement response in patients with fibromyalgia syndrome, and this overreaction may be related to the presence of a persistent terminal injury stimulus. As a result of these stimuli, cutaneous polypoidal injury receptors reflexively release pathological amounts of substance P from nerve endings, which in turn can cause local vasodilation, increased vascular permeability and a form of neurogenic inflammation.
Following the release of substance P from nerve endings, primary sensory neurons in the dorsal root ganglion synthesize more substance P in order to maintain a constant level. The synthesized substance P is transmitted in both directions to the terminals and to the center, thus increasing the level of substance P in the central nervous system. Due to its slow but long-lasting and strong excitatory effect, the central nervous system must be affected to some extent.
It has also been found that in the presence of normal or high levels of 5-HT, substance P has a blocking effect on the release of sensory nerve impulses. In the absence of 5-HT, it will lose this control role, leading to pain hypersensitivity.
3.Immune disorder
Some authors have reported deposits of immunoreactive substances at the dermal-epidermal junction in patients with fibromyalgia syndrome, and electron microscopic observation revealed swelling of muscle capillary endothelial cells in patients with fibromyalgia syndrome, suggesting acute vascular injury; tissue hypoxia and increased permeability. The unexplained weight gain, diffuse swelling of the hands and increased nocturia often reported by patients may be related to increased permeability.
In addition, preliminary studies have found that interleukin-2 (IL-2) levels are elevated in fibromyalgia syndrome. Patients with tumors treated with IL-2 are born with fibromyalgia syndrome-like symptoms, including widespread pain, sleep disturbances, morning stiffness, and the appearance of pressure points. Alpha interferon has also been found to cause fatigue. The above phenomena suggest immune regulation disorders. Abnormal cytokine levels in the body may be associated with the onset of fibromyalgia syndrome.
Epidemiology
The epidemiology of fibromyalgia syndrome has not been reported in China, and there are no precise statistics abroad, but from some preliminary data, it seems that the disease is not uncommon. A survey in the United Kingdom shows that 10.9% of the people who are unable to work due to illness are caused by rheumatic diseases, of which fibromyalgia syndrome accounts for about half. The American Rheumatism Association points out that primary fibromyalgia syndrome is one of the most common rheumatic diseases, taking the third place after RA and OA.
Yunus et al. treated a total of 285 patients with skeletal muscle system disorders in 1 year, of which 29% were OA, 20% were primary fibromyalgia syndrome, and 16% were RA. Among Asian countries, a report from Japan illustrates that they treated a total of 182 patients with rheumatic diseases in connective tissue disease clinics in 2 years, of which 11 cases were fibromyalgia syndrome, accounting for 6% of the total. It ranked seventh after rheumatoid arthritis (27.5%), systemic lupus erythematosus (16%), systemic sclerosis (10.4%), and dry syndrome (7.7%).