Question

Define fibromyalgia and describe the pathophysiology, clinical manifestations, evaluation, and treatment. Comment on advances in diagnosis and management of this disorder that debunk the idea that the disorder is “in the patient’s head.”

Answer 1

Fibromyalgia (FM) is a medical condition characterized by chronic widespread pain and a heightened pain response to pressure.Other symptoms include tiredness to a degree that normal activities are affected, sleep problems and troubles with memory.Some people also report restless legs syndrome, bowel or bladder problems, numbness and tingling and sensitivity to noise, lights or temperature. Fibromyalgia is frequently associated with depression, anxiety and posttraumatic stress disorder.Other types of chronic pain are also frequently present.

Pathophysiology:

Pain processing abnormalitie

Abnormalities in the ascending and descending pathways involved in processing pain have been observed in fibromyalgia. Fifty percent less stimulus is needed to evoke pain in those with fibromyalgia.^[49] A proposed mechanism for chronic pain is sensitization of secondary pain neurons mediated by increased release of proinflammatory cytokines and nitric oxide by glial cells.^[50] Inconsistent reports of decreased serum and CSF values of serotoninhave been observed. There is also some data that suggests altered dopaminergic and noradrenergic signaling in fibromyalgia.^[51]Supporting the monoamine related theories is the efficacy of monoaminergic antidepressantsin fibromyalgia.^[52][53]

Neuroendocrine system

Studies on the neuroendocrine system and HPA axis in fibromyalgia have been inconsistent. One study found fibromyalgia patients exhibited higher plasma cortisol, more extreme peaks and troughs, and higher rates of dexamethasone non suppression. However, other studies have only found correlations between a higher cortisol awakening responseand pain, and not any other abnormalities in cortisol.^[49] Increased baseline ACTH and increase in response to stress have been observed, hypothesized to be a result of decreased negative feedback.^[51]

Autonomic nervous systemEdit

Autonomic nervous system abnormalities have been observed in fibromyalgia, including decreased vasoconstriction response, increased drop in blood pressure and worsening of symptoms in response to tilt table test, and decreased heart rate variability. Heart rate variabilities observed were different in males and females.^[49]

Sleep

Disrupted sleep, insomnia, and poor-quality sleep occur frequently in FM, and may contribute to pain by decreased release of IGF-1 and human growth hormone, leading to decreased tissue repair. Restorative sleep was correlated with improvement in pain related symptoms.^[49]

Neuroimaging

Neuroimaging studies have observed decreased levels of N-acetylaspartic acid(NAA) in the hippocampus of people with fibromyalgia, indicating decreased neuron functionality in this region. Altered connectivity and decreased grey matter of the default mode network,^[54] the insula, and executive attention network have been found in fibromyalgia. Increased levels of glutamate and glutaminehave been observed in the amygdala, parts of the prefrontal cortex, the posterior cingulate cortex, and the insula, correlating with pain levels in FM. Decreased GABA has been observed in the anterior insular in fibromyalgia. However, neuroimaging studies, in particular neurochemical imaging studies, are limited by methodology and interpretation.^[55] Increased cerebral blood flow in response to pain was found in one fMRI study.^[50] Findings of decreased blood flow in the thalamus and other regions of the basal ganglia correlating with treatment have been relatively consistent over three studies. Decreased binding of μ-opioid receptor have been observed; however, it is unknown if this is a result of increased endogenous binding in response to pain, or down regulation.^[51]

Inflammation and immune system

Overlaps have been drawn between chronic fatigue syndrome and fibromyalgia. One study found increased levels of pro-inflammatory cytokines in fibromyalgia, which may increase sensitivity to pain, and contribute to mood problems. Increased levels of IL-1RA, Interleukin 6 and Interleukin 8 have been found.^[ Neurogenic inflammation has been proposed as a contributing factor to fibromyalgia  A systematic review found most cytokines levels were similar in patients and controls, except for IL-1 receptor antagonist, IL-6 and IL-8.

The defining symptoms of fibromyalgia are chronic widespread pain, fatigue, sleep disturbance, and heightened pain in response to tactile pressure (allodynia) Other symptoms may include tingling of the skin (paresthesias), prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching, palpitations, and functional bowel disturbances.

Many people experience cognitive dysfunction^[1 (known as "fibrofog"), which may be characterized by impaired concentration, problems with short and long-term memory, short-term memory consolidation, impaired speed of performance,  inability to multi-task, cognitive overload, and diminished attention span. Fibromyalgia is often associated with anxiety and depressivesymptoms

Other symptoms often attributed to fibromyalgia that may be due to a comorbiddisorder include myofascial pain syndrome, also referred to as chronic myofascial pain, diffuse non-dermatomal paresthesias, functional bowel disturbances and irritable bowel syndrome, genitourinary symptoms and interstitial cystitis, dermatological disorders, headaches, myoclonic twitches, and symptomatic low blood sugar. Although fibromyalgia is classified based on the presence of chronic widespread pain, pain may also be localized in areas such as the shoulders, neck, low back, hips, or other areas. Many sufferers also experience varying degrees of myofascial pain and have high rates of comorbid temporomandibular joint dysfunction. 20–30% of people with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.

Evaluation:

• Revised Fibromyalgia Impact Questionnaire^[65]
• Widespread Pain Index^[66]
• Hospital Anxiety and Depression Scale
• Multiple Ability Self-Report Questionnaire^[67]
• Multidimensional Fatigue Inventory
• Medical Outcomes Study Sleep Scale

Treatment :

Medical attention is needed because fibromyalgia can be difficult to manage. As it is a syndrome, each patient will experience a different set of symptoms, and an individual treatment plan will be necessary.

Treatment may include some or all of the following:

• an active exercise program
• acupuncture
• psychotherapy
• behavior modification therapy
• chiropractic care
• massage
• physical therapy
• low-dose anti-depressants, although these are not a first-line treatment

People with fibromyalgia need to work with their doctor to come up with a treatment plan that provides the best results.

Drugs

Drugs may be recommended to treat certain symptoms.

These may include over-the-counter (OTC) pain relievers. However, the European League Against Rheumatism (EULAR) issued a recommendation against using non-steroidal anti-inflammatory drugs (NSAIDs) to treat fibromyalgia in their updated 2016 guidelines.

Antidepressants, such as duloxetine, or Cymbalta, and milnacipran, or Savella, may help reduce pain. Anti-seizure drugs, such as gabapentin also known as Neurontin, and pregabalin, or Lyrica, may be prescribed.

Exercise

A combination of aerobic exercise and resistance training, or strength training, has been linked to a reduction in painTrusted Source, tenderness, stiffness, and sleep disturbance, in some patients.

If exercise is helping with symptoms, it is important to maintain consistency in order to see progress. Working out with a partner or personal trainer may help to keep the exercise program active.

Acupuncture

Some patients have experienced improvements in their quality of life after starting acupuncture therapy for fibromyalgia. The number of sessions required will depend on the symptoms and their severity.

Behavior modification therapy

Behavior modification therapy is a form of cognitive behavioral therapy (CBT) that aims to reduce negative, stress- or pain-increasing behaviors and improve positive, mindful behaviors. It includes learning new coping skills and relaxation exercises.