Our evolving understanding of the potential causes of fibromyalgia, and its placement along a continuum of related conditions, informs an individualized treatment approach.
Dmitry M. Arbuck, MD
Diagnostic criteria for fibromyalgia were initially established by the American College of Rheumatology in 1990,1 with revised criteria published in May 2010.2 Our understanding of the underlying mechanisms and treatment of fibromyalgia underwent a significant evolution in the 20 years between publication of these criteria. The 1990 criteria emphasized the diffuse body pain associated with fibromyalgia, but lacked perspective on the degree of central nervous system involvement in pain perception and the corresponding phenomena of fatigue, sleep deficiency, decrease in mental function, forgetfulness, and decrease in general function associated with fibromyalgia. The number of tender points that formed the foundation of diagnosis (11 out of 18) was arbitrary and non-specific, as well as confusing because fibromyalgia tender points are tender in practically every individual suffering from chronic diffuse pain. Also, the 1990 criteria did not include a mechanism for measuring symptom severity. The 2010 criteria measure fatigue, cognitive impairment, and waking unrefreshed, as well as somatic complaints such as numbness, dizziness, nausea, irritable bowel syndrome, and depression. In the latest classification, the patient has to have pain in seven or more areas of the body out of 19 specified areas and a symptom severity score of 5 or more, or pain in three to six areas and a symptom severity of 9 or more for a diagnosis. The pain has to be present for at least three months with no other disorder that would otherwise explain the pain.2 Obviously, the diagnosis of fibromyalgia is still descriptive and is not based on underlying pathology. It is still seen as a rheumatologic rather than neuropsychiatric condition.
Any clinician who regularly deals with fibromyalgia understands that it is a syndrome, not a disease, and that it is based not in the muscles and tendons, but in the central nervous system, and expresses pathology of pain perception rather than a peripheral abnormal process.3 At the same time, the peripheral tissues and organs may be triggers for the central abnormal process. As a result, due to the underlying nature of the pathology, fibromyalgia may be part of a larger dysregulation spectrum syndrome that includes conditions with a high degree of comorbidity such as chronic fatigue syndrome, irritable bladder, irritable bowel syndrome, interstitial cystitis, restless leg syndrome, tension headaches, migraines, dysmenorrhea, temporomandibular joint disorder, depression, anxiety, insomnia, and PTSD.4
Fibromyalgia is associated with a range of triggers
The diagnosis of fibromyalgia is established clinically.5 Although fibromyalgia syndrome represents primarily central nervous system dysfunction, understanding the various potential triggers of this condition will inform treatment decisions. Fibromyalgia triggers may be grouped into several categories:
Cervical triggers may include cervical stenosis, cervical facet arthropathy, cervical disk herniation, foraminal stenosis, and myofacial syndrome,6 among other structural problems in the neck. There is no direct relationship between the severity of cervical pathology and the severity of fibromyalgia symptoms. After appropriate treatment, the general body pain usually disappears, while local cervical pain persists to various degrees. A possible theory explaining this phenomenon may be interference with the conduction of pain-related information through the spinal cord on a cervical level. Trigeminal nerve stimulation also may be a factor associated with stimulation of the upper cervical roots, and with secondary activation of the trigeminal nucleus caudalis, which extends into the upper segment of the cervical spinal cord.7 This may be connected to the cause of frequent headaches in fibromyalgia.
Metabolic/endocrine problems are extremely variable and are associated with high CO2, low O2, low iron, high estrogen levels, and low levels of growth hormone, testosterone, thyroid, and omega III acid.8,9 They can also be associated with adrenal insufficiency, Cushing’s syndrome, hypopituitarism, food additives, caffeine, vitamin D deficiency, and vitamin B-group deficiency.10 Many of these conditions are correctable and looking into their causes must be part of a thorough fibromyalgia evaluation. Unfortunately, fibromyalgia symptoms often do not improve after metabolic/endocrine deficiencies are corrected. Although addressing or removing these triggers may not be sufficient for pain improvement, it nevertheless it is an integral step in addressing the central nervous system mechanisms associated with fibromyalgia. Metabolic/endocrine problems may be involved in the overload of the central processing of painful stimuli. Pain perception involved in the formation of central sensitization and upregulating of the central alert system pathologically develops faulty identification of sub-threshold impulses as pain.
Several inflammatory/autoimmune conditions are associated with fibromyalgia symptoms, including Epstein-Barr and cytomegalovirus infections, hepatitis B and C, myositis, multiple sclerosis, and celiac disease, Lyme disease, and polymyalgia rheumatica.11 Nearly half of patients with Sjögren’s syndrome may also exhibit symptoms of fibromyalgia; about 25% of patients with systemic lupus erythematosis and rheumatoid arthritis do, as well.12,13 Researchers have also reported an association between fibromyalgia symptoms and an increase in the number of natural killer cells and tumor necrosis factor-alpha.14 When considering these possible related conditions, it is prudent to remember that they represent triggers of fibromyalgia symptoms but do not explain them. The pathological process that occurs due to inflammatory or autoimmune reactions is similar to what happens in metabolic and endocrine events with either gradual or acute overload of the central pain perception mechanisms.
Fibromyalgia etiology may be grouped in several major blocks:
Peripheral and central nervous system problems are also salient in fibromyalgia. Involvement of NMDA receptors, serotonin, dopamine, and norepinephrine, as well as GABA, has been reported.15-17 Therefore, depression, anxiety, insomnia, and PTSD are commonly comorbid with fibromyalgia.18 Hypochondriasis, somatization, and somatictype psychosis may also be observed in fibromyalgia patients.19
A possible explanation of the central nervous system dysregulation seen in fibromyalgia may be that there is chronic or acute overload of central pain processes due to an increase of dopamine and endorphin levels that do not subside after harmful inferences disappear. Therefore, in pathological self protection, the brain tries to keep dopamine and endorphin levels high by dropping pain and stress thresholds. By doing that, hyperalgesia pathologically maintains high levels of dopamine and endorphins, which is associated with pathological gratification from harmful inferences. Those symptoms tightly overlap with PTSD, self-mutilation, battered woman and child syndrome, and central neuropathic pain.20
Treatment should be individualized
Fibromyalgia syndrome should be thought of as a continuum of dysfunction in various structures involved in the pathological process, including muscles/tendons, nociceptors, nerve trunks, the spinal cord, deep brain structures, and the cortex. These structures may be influenced by the various triggers reviewed in this article and are involved to varying degrees in highly patient-specific ways. Therefore, treatment must focus on trying to influence the specific areas of this continuum that are more involved in the particular patient. Topical preparations, nerve blocks, medications that modulate spinal signal transmission, and brain-modulating medications may be used in attempts to address relevant triggers.
Dmitry Arbuck, MD, is a psychiatrist specializing in pain management. He a member of the Pain Management editorial board and president of Meridian Health Group, a multidisciplinary pain management practice (www.meridianhealthgroup.com).
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