It is quite difficult to diagnose fibromyalgia because there is no single biologically significant cause. Despite the use of two criteria-based and clinical methods for diagnosis, FM continues to be a controversial interpretation. Some studies suggest that fibromyalgia is overdiagnosed, and others report that community physicians have limited knowledge of FM diagnosis and criteria.
Criterion Based Diagnosis
Fibromyalgia was formally established by official criteria in 1990, after which numerous symptoms have become a central component of the disease. There is now evidence to support fibromyalgia as a dimensional or persistent disorder and has been included in the World Health Organization’s list of international diseases. In 2016, the common dye criterion was re-established and therefore some criteria are required for diagnosing fibromyalgia and these are as follows:
• Common pain index (WPI) 7 and symptom severity scale (SSS) 5 or WPI 4–6 and SSS score 9,
• Presence of widespread pain (pain in four or five body parts),
• Symptoms lasting at least 3 months,
Classification criteria can help guide a diagnosis, but are primarily useful for research and epidemiological studies.
Clinical diagnosis is based on the relationship between patients and patients, and due to the intensity of the symptoms, chronic widespread pain prevails. Some of these intense symptoms are as follows:
• Abdominal cramps,
• Sleeping disorder,
• muscle spasms,
• muscle stiffness,
• Decreased physical, social and cognitive functions,
Depressed mood, anxiety, and irritability
Moreover, FM differs from chronic widespread pain in that fatigue includes painless symptoms including measures of severity, unrefreshed sleep, cognitive problems, and somatic symptoms. There are common symptoms in fibromyalgia and these are:
Hyperalgesia, hypersensitivity to a normally painful stimulus such as pressure,
Allodynia, painful sensation to a normally painless stimulus, such as touch and massage,
Enlargement of the recipient area, pain beyond the area
Peripheral nerve supply,
• Prolonged electrophysiological discharge,
The unpleasant aftertaste quality of the pain such as burning, throbbing, tingling or numbness,
However, it causes pain along more than one spinal segment leading to chronic widespread pain. The number of pain zones correlates strongly with the somatic and psychological symptom burden in the general population. Quantitative sensory testing should be performed to determine whether an enhanced response is present using pressure, needle stick, cold, heat, vibration, electrical, ischemia, and chemical (capsaicin, hypertonic saline) stimuli. Patients should be tested for allodynia (using cotton swabs, brushes, Von Frey filaments), transient aggregation, conditioned pain modulation, and nociceptive flexion reflex. All common conditions such as depression or fibromyalgia remain in a dilemma of the disease state (health) and trait (characteristic that distinguishes a particular person) versus the disease state.
Given the high incidence of chronic pain, understanding the underlying processes underlying such pain is essential. Repeated stimulation of the centripetal nerves causes changes in the way pain signals are processed, leading to a pathophysiological state in which the nervous system becomes sensitive, while the perception of pain increases. Both the peripheral and central nervous system can become sensitive to pain signals in response to injury or inflammatory nociceptors. The environment may become more sensitive to painful stimuli, a process called peripheral sensitization. These sensitize the nociceptors and then send additional pain signals to the central nervous system (CNS), leading to overstimulation of the CNS.
Central sensitization leads to neuronal irregularity and overstimulation by disorganization in the central nervous system (imbalance between pain transmission and pain prevention). For this reason, it is a physiological phenomenon that causes hypersensitivity to both harmful and non-harmful stimuli and continues pain. Activated C fibers refer to several neurotransmitters in the nerve terminals and they are as follows:
• Substance P (SP),
Nerve growth factor (NGF),
• Calcitonin gene related peptide,
Vasoactive intestinal peptide,
• Glutamate (GLUT),
Neurotrophic factors derived from the brain,
These chemicals in the body cause a wave of excitation at the synapse that hyperexcites the postsynaptic receptors. Some of these chemicals in the body are as follows:
• N-methyl-D-aspartate (NMDA),
• Metabotropic glutamate,
• Tyrosine kinase B (TrK-B)
• Protein kinaz gama,
While activation of these receptors causes a remarkable physiological change in postsynaptic nerve cells, these physiological changes are as follows:
• Dice changes,
• Intracellular flow of calcium,
Protein kinase activation
Protein c-fos expression (marker for neuronal activity following peripheral stimulation),
These changes seen cause an intensification of the hyper-excitability of second-order neurons, leading to hypersensitivity to various peripheral stimuli. Central sensitivity occurs when confusion occurs in the processing of central sensory information that enhances the central nervous system’s response to a peripheral input. Central sensitization has been proposed as the main etiology for central sensitivity syndromes (CSS), which refer to a medically uncertain group of disorders with no organic cause. Some authors state that their symptoms cannot be explained medically and are psychiatric, psychological, or psychosocial in nature. Therefore, people with fibromyalgia suffer from abnormalities in central pain processing.
A lower threshold for interpreting sensory information as harmful means in addition to an increased stimulation mechanism or reduced inhibition mechanisms. This plays an important role in the development and maintenance of chronic pain. On the other hand, some abnormalities of the peripheral nervous system as an antidromal axonal reflex of C fibers in response to a stimulus can initiate neuroendocrine processes and vascular permeability. These processes include the phenomenon of neuroinflammation, in which stress and other psychological factors induce these neural responses to enhance the perception of pain. Abnormal sensory and pain processing is a key factor in the pathophysiology of fibromyalgia and, in addition, sensitization increases the perception of pain.
Factors Causing Fibromyalgia
There is evidence of pain-related excessive neuronal activity at multiple levels of the central nervous system, structural and functional changes in the brain with imaging studies, or impaired function of normal declining inhibitory mechanisms. However, other factors causing fibromyalgia are as follows:
Genetic predisposition or change in the expression of various genes (epigenetic mechanisms),
Deficiencies in neurotransmitter levels,
Biochemical changes in the body,
Certain types of infections e.g. various factors such as epstein-barr virus, Lyme disease and Q fever, viral hepatitis,
• Mood disorders,
• Sociocultural environment (early life stress or boredom),
Past experiences in general, such as childhood or sexual abuse,
Sensitivity and subcortical nociceptive transmission,
Genes associated with increased and decreased frequency of chronic pain conditions or pain sensitivity regulate the breakdown or binding of neurotransmitters and other inflammatory pathways that modulate pain sensitivity. The causative genes involved in fibromyalgia include genes that control serotonin mechanisms, dopamine receptors, and also the metabolism of catecholamines. In a review, neurobiological substrates, including the hypothalamic-pituitary-adrenal (HPA) axis, monoaminergic, opioidergic, endocannabinoid, and immune systems, as well as some epigenetic mechanisms, have been associated with the risk of early life psychological stress and chronic pain in later life.
Early psychological trauma can alter the HPA axis response, resulting in dysfunction of peripheral and spinal dorsal horn neurons in a central sensitization syndrome, excitatory amino acids, and central neuropeptides that can lead to abnormal nociceptive input to the brain in the absence of a true painful stimulation. Similarly, anxiety, depression, and post-traumatic stress disorder occur in many people with FM who are exposed to early abuse. Patients with FM appear to have specific gut microbiome changes that differ from their healthy peers. Clos-García and his team recently found a change in glutamate metabolism (a possible molecular biomarker) that connects the gut microbiome to the brain via the enteric nervous system. This change has been associated with psychiatric and gastrointestinal disorders. Finally, there is no scientific support for the idea that physical trauma causes FM, for example motor vehicle accidents.
Other Central Sensitivity Syndromes
Pain, fatigue, and other distressing sensations that occur in the absence of clinically significant pathology are common health problems in medical practice. Such experiences are never uniform, but symptoms often coexist in stereotypically recognizable ways. Several criteria have been proposed for classifying a disease as a member of the CSS group. These criteria are as follows:
• The presence of CS,
• Absence of an underlying disease (primary conditions)
• The interrelation between the disorders,
However, the differential diagnosis of FM is difficult due to the interrelationships between the disorders. In addition, in the studies conducted by Yunus and his team, they reported a number of ailments included in the CSS family list, and these are as follows:
Irritable bowel syndrome,
Primary (dysfunctional) dyspepsia,
Tension type headache,
Myofascial pain syndrome,
Myofascial temporomandibular disorder,
Primary chronic neck pain,
Primary back pain, restless legs syndrome, among others
Periodic limb movement disorder,
Since fibromyalgia patients report many symptoms, the symptoms appear very severe, unusual, and patients are very healthy compared to patients with other pain disorders. A recent clinical review reported that 62% of FM patients showed major depressive disorder, 11% bipolar disorder, 29% panic disorder, and 29% social phobia. Mental disorders, particularly mood disorders, have been associated with a negative impact on pain, fatigue, sleep, physical function, and quality of life in FM.
It is reported that non-arthritic rheumatism often includes anxiety states. Musculoskeletal pain or fatigue associated with other disorders can mimic those of FM and vice versa. In addition, there are many similar disorders other than FM that overlap simultaneously, and these broad categories are as follows:
Inflammatory and autoimmune disorders including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, polymyalgia rheumatica and spondyloarthritis,
Muscular disorders and myalgias,
Myofascial pain syndrome, temporomandibular joint dysfunction and low back pain
Writer: Ozlem Guvenc Agaoglu