Pathophysiology Of Fibromyalgia. Include Clinical Manifestations, Evaluation, & Treatment.
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Pathophysiology of Fibromyalgia
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Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive impairment and mood disorders. The prevalence of FM is estimated to be between 2 and 8% of the general population, with a higher proportion of women than men affected . The etiology and pathophysiology of FM are not fully understood, but several factors have been proposed to play a role, such as genetic predisposition, environmental triggers, altered pain processing in the central nervous system (CNS), peripheral pain mechanisms, neuroendocrine and autonomic dysregulation, psychological factors and comorbid conditions .
Genetic Predisposition
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FM tends to run in families, suggesting that genetic factors may influence the susceptibility to developing the disorder. Several studies have identified polymorphisms in genes encoding for neurotransmitters, receptors, enzymes and transporters involved in pain modulation, such as serotonin, dopamine, norepinephrine, opioid, glutamate and cannabinoid systems . However, the results are inconsistent and the effect sizes are small, indicating that FM is likely a polygenic disorder with multiple genes interacting with environmental factors .
Environmental Triggers
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Several physical and psychological stressors have been reported to trigger or exacerbate FM symptoms in some patients. These include infections (such as viral illnesses or Lyme disease), trauma (such as physical injury or surgery), emotional stress (such as abuse or bereavement), hormonal changes (such as menopause or pregnancy) and lifestyle factors (such as obesity, smoking or sedentary behavior) . The mechanisms by which these triggers may contribute to FM are not clear, but they may involve immune activation, inflammation, oxidative stress, epigenetic changes or neuroplasticity .
Altered Pain Processing in the CNS
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One of the main features of FM is the heightened sensitivity to pain, also known as hyperalgesia. This means that patients with FM experience pain from stimuli that are normally not painful (allodynia) or more pain from stimuli that are mildly painful (hyperesthesia). This abnormal pain perception is thought to result from an imbalance between the excitatory and inhibitory pathways that modulate pain signals in the CNS . Several neuroimaging studies have shown increased activity in brain regions involved in pain processing, such as the anterior cingulate cortex, insula, thalamus and somatosensory cortex, in response to various painful stimuli in patients with FM compared with healthy controls . Moreover, reduced levels of neurotransmitters that inhibit pain transmission, such as serotonin, norepinephrine and endogenous opioids, have been found in the cerebrospinal fluid and brain tissue of patients with FM . Conversely, increased levels of neurotransmitters that facilitate pain transmission, such as glutamate, substance P and nerve growth factor, have been detected in the same biological fluids of patients with FM . These findings suggest that FM is associated with a state of central sensitization, which is defined as an amplification of neural signaling within the CNS resulting in pain hypersensitivity .
Peripheral Pain Mechanisms
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In addition to central sensitization, peripheral pain mechanisms may also contribute to FM symptoms in some patients. These include neuropathic pain and nociceptive pain. Neuropathic pain is caused by damage or dysfunction of the peripheral nerves or nerve endings. Several studies have reported evidence of small fiber neuropathy (SFN) in a subset of patients with FM. SFN is characterized by reduced density and function of small nerve fibers that mediate thermal and pain sensations . SFN may result from various causes, such as diabetes mellitus, autoimmune diseases or genetic mutations . Nociceptive pain is caused by stimulation of nociceptors, which are sensory receptors that respond to tissue damage or inflammation. Some patients with FM may have coexisting conditions that cause nociceptive pain, such as osteoarthritis,
rheumatoid arthritis or irritable bowel syndrome .
Neuroendocrine and Autonomic Dysregulation
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Another feature of FM is the dysregulation of the neuroendocrine and autonomic systems that regulate various physiological functions, such as stress response, sleep quality, mood regulation and immune function . Several studies have shown abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis activity in patients with FM. The HPA axis is responsible for producing cortisol and other hormones that help the body cope with stress. Patients with FM tend to have lower levels of cortisol and higher levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in the blood and urine, indicating a blunted or impaired HPA axis response to stress . Moreover, patients with FM have altered levels of growth hormone, melatonin, thyroid hormones and sex hormones, which may affect various aspects of health, such as growth, metabolism, reproduction and circadian rhythms . Furthermore, patients with FM have evidence of autonomic nervous system dysfunction, which controls the involuntary functions of the body, such as heart rate, blood pressure, digestion and sweating. Patients with FM tend to have increased sympathetic activity and decreased parasympathetic activity, resulting in symptoms such as tachycardia, orthostatic hypotension, gastrointestinal motility disorders and thermoregulatory disturbances .
Psychological Factors and Comorbid Conditions
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FM is often accompanied by psychological factors and comorbid conditions that may influence the severity and impact of the disorder. These include anxiety, depression, post-traumatic stress disorder (PTSD), cognitive impairment (also known as fibro fog), sleep disorders, chronic fatigue syndrome, migraine, temporomandibular joint disorder (TMJ), interstitial cystitis and restless legs syndrome . The relationship between these factors and conditions and FM is complex and bidirectional. On one hand, they may act as triggers or aggravators of FM symptoms by increasing stress levels, impairing coping skills or interfering with treatment adherence. On the other hand, they may be consequences or complications of FM symptoms by affecting quality of life, social functioning or psychological well-being .
Evaluation and Treatment
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The diagnosis of FM is based on clinical criteria that include the presence of chronic widespread pain for at least three months and the exclusion of other conditions that may cause similar symptoms . There are no specific laboratory tests or imaging studies that can confirm or rule out FM. However, some tests may be performed to assess the general health status of the patient or to screen for potential comorbidities or differential diagnoses . The treatment of FM is multidisciplinary and individualized, depending on the patient’s needs and preferences. The main goals of treatment are to reduce pain and other symptoms, improve physical function and quality of life, enhance coping skills and self-management strategies, and prevent or treat comorbid conditions . The treatment options include pharmacological and non-pharmacological interventions. Pharmacological interventions include analgesics (such as acetaminophen, nonsteroidal anti-inflammatory drugs or opioids), antidepressants (such as duloxetine, milnacipran or amitriptyline), anticonvulsants (such as pregabalin or gabapentin) and muscle relaxants (such as cyclobenzaprine or tizanidine) . Non-pharmacological interventions include exercise (such as aerobic exercise, strength training or tai chi), cognitive-behavioral therapy (CBT), education, relaxation techniques (such as meditation, biofeedback or hypnosis), acupuncture,
massage therapy, hydrotherapy and dietary supplements (such as vitamin D, magnesium or omega-3 fatty acids) . The effectiveness of these interventions varies from patient to patient and may depend on several factors, such as adherence, motivation, expectations and side effects. Therefore, a shared decision-making approach between the patient and the clinician is recommended to select the most appropriate and acceptable treatment plan for each individual case .
Bibliography
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