Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc.
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PMID:Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. 1711

Short-term stressors, capable of increasing nitric oxide levels, act to initiate cases of illnesses including chronic fatigue syndrome, multiple chemical sensitivity, fibromyalgia and posttraumatic stress disorder. These stressors, acting primarily through the nitric oxide product, peroxynitrite, are thought to initiate a complex vicious cycle mechanism, known as the NO/ONOO- cycle that is responsible for chronic illness. The complexity of the NO/ONOO- cycle raises the question as to whether the mechanism that switches on this cycle is this complex cycle itself or whether a simpler mechanism is the primary switch. It is proposed here that the switch involves a combination of two variable switches, the increase of nitric oxide synthase (NOS) activity and the partial uncoupling of the NOS activity, with uncoupling caused by a tetrahydrobiopterin (BH4) deficiency. NOS uncoupling causes the NOS enzymes to produce superoxide, the other precursor of peroxynitrite, in place of nitric oxide. Thus partial uncoupling will cause NOS proteins to act like peroxynitrite synthases, leading, in turn to increased NF-kappaB activity. Peroxynitrite is known to oxidize BH4, and consequently partial uncoupling may initiate a vicious cycle, propagating the partial uncoupling over time. The combination of high NOS activity and BH4 depletion will lead to a potential vicious cycle that may be expected to switch on the larger NO/ONOO- cycle, thus producing the symptoms and signs of chronic illness. The role of peroxynitrite in the NO/ONOO- cycle also implies that such uncoupling is part of the chronic phase cycle mechanism such that agents that lower uncoupling will be useful in treatment.
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PMID:Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO- cycle. 1744 11

We proposed to assess antioxidant status and nitric oxide in fibromyalgia (FM) patients in comparison to healthy controls. Additionally, the association between the serum antioxidant levels and clinical findings in FM patients was also investigated. Thirty-seven FM patients and 37 healthy controls were enrolled in this study. Severity of fatigue and pain were determined by Visual Analogue Scale. Functional capacity in daily living activities was evaluated by fibromyalgia impact questionnaire. Serum NO, catalase and glutathione were measured. Serum glutathione and catalase levels were significantly lower in FM patients than controls. However, no significant difference was seen in serum NO levels between the two groups. A significant correlation was evident between serum NO level and pain. Additionally, the correlation between glutathione level and morning stiffness was found to be significant. These findings support other studies, we assume that these two antioxidants might have impact on the pathogenesis of FM disease.
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PMID:Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study. 1885 66

The etiology of fibromyalgia is not clearly understood. In recent years, a few studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of fibromyalgia. The aim of this study was to investigate plasma antioxidant vitamins, lipid peroxidation (LP), and nitric oxide (NO) levels in patients with fibromyalgia and controls. The study was performed on the blood plasma of 30 female patients and 30 age-matched controls. After a fast of 12 h, blood samples were taken, and plasma samples were obtained for measurement of vitamins A, C, E, and beta-carotene concentrations and levels of LP and NO. Concentrations of vitamins A (p < 0.01) and E (p < 0.001) were significantly lower in patients with fibromyalgia than in controls, and LP levels were significantly (p < 0.05) higher in the plasma of the patients than in controls. Concentrations of vitamin C and beta-carotene and levels of NO did not change significantly. These results provide some evidence for a potential role of LP and fat-soluble antioxidants in the patients with fibromyalgia.
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PMID:Levels of lipid peroxidation, nitric oxide, and antioxidant vitamins in plasma of patients with fibromyalgia. 1931 26

Inadequately treated acute and chronic pain remains a major cause of suffering and dissatisfaction in pain therapy. A cause for the variable success of pharmacologic pain therapy is the different genetic disposition of patients to develop pain or to respond to analgesics. The patient's phenotype may be regarded as the result of synergistic or antagonistic effects of several genetic variants concomitantly present in an individual. Variants modulate the risk of developing painful disease or its clinical course (e.g., migraine, fibromyalgia, low back pain). Other variants modulate the perception of pain (e.g., OPRM1 or GCH1 variants conferring modest pain protection by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation). Other polymorphisms alter pharmacokinetic mechanisms controlling the local availability of active analgesic molecules at their effector sites (e.g., decreased CYP2D6 related prodrug activation of codeine to morphine). In addition, genetic variants may alter pharmacodynamic mechanisms controlling the interaction of the analgesic molecules with their target structures (e.g., opioid receptor mutations). Finally, opioid dosage requirements may be increased depending on the risk of drug addiction (e.g., DRD2 polymorphisms decreasing the functioning of the dopaminergic reward system). With the complex nature of pain involving various mechanisms of nociception, drug action, drug pharmacology, pain disease and possibly substance addiction, a multigenic or even genome wide approach to genetics could be required to base individualized pain therapy on the patient's genotype.
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PMID:Genetic modulation of the pharmacological treatment of pain. 1961 6

Fibromyalgia syndrome (FMS) is characterised by diffuse muscle pain, poor sleep and unrelenting fatigue. Individuals with FMS may also experience headaches, anxiety, depression, poor memory, numbness and tingling in the extremities, cold hands and feet, irritable bowel syndrome and lowered immune function. FMS is a common chronic pain syndrome of unknown etiology and limited treatment options. Previous studies have reported oxidative stress in FMS patients, but the results were inconsistent. Oxidative stress and nitric oxide is involved in FMS pathophysiology, however, it is still not clear whether oxidative stress abnormalities are the cause of FMS. There are several studies indicating oxidative stress in patients with FMS. Oxidant (Malondialdehyde) and antioxidant (Superoxide dismutase) balances were found to be changed in FMS patients. Furthermore, increased free radical levels may be responsible for the development of FMS and free radical-mediated oxidative stress including inflammatory cytokines may also play important roles in its pathogenesis. Moreover, oxidative stress is supposed to be increased in patients with FMS which is related to the severity of FMS symptoms. Therefore, it is important to understand whether the oxidative stress parameters are involved in FMS and what is the relationship between these and antioxidants in FMS patients. In this review we will elucidate the importance of oxidative stress and antioxidants and its possible relationship with FMS. Moreover, as metal toxicity is also reported to be involved in the pathogenesis of FMS, therefore we will also try to establish the role of toxic metals in the pathogenesis of FMS.
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PMID:Oxidative stress and antioxidative parameters and metal ion content in patients with fibromyalgia syndrome: implications in the pathogenesis of the disease. 2437 71

The aims of this study were to investigate the effect of exercise therapy on the oxidative stress in fibromyalgia patients and relationship between oxidative stress and fibromyalgia symptoms. Thirty women diagnosed with fibromyalgia according to the American College of Rheumatology preliminary criteria, and 23 healthy women whose age- and weight-matched women were enrolled the study. Pain intensity with visual analog scale (VAS), the number of tender points, the fibromyalgia impact questionnaire (FIQ), the Beck depression inventory (BDI) were evaluated. The oxidative stress parameters thiobarbituric acid reactive substances, protein carbonyls, and nitric oxide, and antioxidant parameters thiols and catalase were investigated in patients and control group. After, combined aerobic and strengthen exercise regimen was given to fibromyalgia group. Exercise therapy consisted of a warming period of 10 min, aerobic exercises period of 20 min, muscle strengthening exercises for 20 min, and 10 min cooling down period. Therapy was lasting 1 h three times per week over a 12-week period. All parameters were reevaluated after the treatment in the patient group. The oxidative stress parameters levels were significantly higher, and antioxidant parameters were significantly lower in patients with fibromyalgia than in the controls. VAS, FIQ, and BDI scores decreased significantly with exercise therapy. The exercise improved all parameters of oxidative stress and antioxidant parameters. Also, all clinical parameters were improved with exercise. We should focus on oxidative stress in the treatment for fibromyalgia with the main objective of reducing oxidative load.
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PMID:Effects of 12-week combined exercise therapy on oxidative stress in female fibromyalgia patients. 2461 May 39

Exercise-induced analgesia is a phenomenon discussed worldwide. This effect began to be investigated in the early 1970s in healthy individuals and rodents during and after an acute or chronic session of running or swimming. Thereafter, studies found this effect was also induced by resistance exercises. Over the years, many studies have demonstrated the importance of exercise-induced analgesia in relieving pain caused by different conditions, such as fibromyalgia, low back pain, neuropathy, and osteoarthritis. This review aims to provide the reader with an in-depth description of the main endogenous systems, substances, neurotransmitters, receptors and enzymes that are thought to be involved in the analgesic effect induced by exercise. Many hypotheses have been proposed to elucidate the mechanisms responsible for exercise-induced analgesia. One of the most accepted hypotheses has been the activation of several endogenous systems described as analgesics. Studies have demonstrated that during and after exercise different endogenous systems are activated, which release substances or neurotransmitters, such as opioids, nitric oxide, serotonin, catecholamines and endocannabinoids, that may modulate the pain perception.
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PMID:Endogenous systems involved in exercise-induced analgesia. 2976 16

It is thought that an ill defined biochemical cascade may lead to protracted withdrawal symptoms subsequent to discontinuance of routine use of benzodiazepine class drugs and establish chronic illness in some patients. In this review, published findings are presented that support the novel concept that withdrawal from benzodiazepine class drugs can trigger elevated and sustained levels of a potent oxidant called peroxynitrite via potentiation of the L-type voltage-gated calcium channels, and in the later stages of withdrawal, via excessive N-methyl-D-aspartate receptor activity, as well. Potentiation of L-type voltage-gated calcium channels and excessive N-methyl-D-aspartate receptor activity both result in calcium influx into the cell that triggers nitric oxide synthesis. In pathophysiological conditions, such increased nitric oxide synthesis leads to peroxynitrite formation. The downstream effects of peroxynitrite formation that may occur during withdrawal ultimately lead to further peroxynitrite production in a system of overlapping vicious cycles collectively referred to as the NO/ONOO(-) cycle. Once triggered, the elements of the NO/ONOO(-) cycle perpetuate pathophysiology, perhaps including reduced GABAA receptor functioning, that may explain protracted withdrawal associated symptoms while the vicious cycle nature of the NO/ONOO(-) cycle may explain how withdrawal becomes a chronic state. Suboptimal levels of tetrahydrobiopterin may be one risk factor for the development of the protracted withdrawal syndrome as this will lead to partial nitric oxide uncoupling and resultant peroxynitrite formation. Nitric oxide uncoupling results in superoxide production as calcium-dependent nitric oxide synthases attempt to produce nitric oxide in response to L-type voltage-gated calcium channel-mediated calcium influx that is known to occur during withdrawal. The combination of nitric oxide and superoxide produced, as when partial uncoupling occurs, react together in a very rapid, diffusion limited reaction to form peroxynitrite and thereby trigger the NO/ONOO(-) cycle. The NO/ONOO(-) cycle may explain the nature of the protracted withdrawal syndrome and the related constellation of symptoms that are also common in other illnesses characterized as NO/ONOO(-) disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.
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PMID:How chronic administration of benzodiazepines leads to unexplained chronic illnesses: A hypothesis. 3003 16

Chronic pain is one of the most common clinical presentations in the primary care settings. In the US, Fibromyalgia (FM) affects about 1-3% of adults and commonly occurs in adults between the ages of 40-50 years. FM causes widespread muscular pain and tenderness with hyperalgesia and allodynia and may be associated with other somatic complaints. Hyperbaric oxygen therapy (HBOT) has been utilized and has recently shown promising effects in the management of FM and other chronic pain disorders. In HBOT, the intermittent breathing of 100% oxygen in a pressurized chamber where the pressure is higher than 1 atmosphere absolute (ATA) has been utilized. HBOT exhibits a significant anti-inflammatory effect through reducing production of glial cells and inflammatory mediators which results in pain alleviation in different chronic pain conditions. HBOT can also influence neuroplasticity and affects the mitochondrial mechanisms resulting in functional brain changes. In addition to that, HBOT stimulates nitric oxide (NO) synthesis which helps in alleviating hyperalgesia and NO-dependent release of endogenous opioids which seemed to be the primary HBOT mechanism of antinociception. Moreover, aerobic exercise and meditative movement therapies (MMT) have gained attention for their role in pain alleviation through different anti-inflammatory and antioxidant mechanisms. In this review, we aim to elucidate the different mechanisms of HBOT and aerobic exercise in attenuating pain as adjuvant therapy in the multidisciplinary treatment strategy of chronic pain, and more particularly fibromyalgia.
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PMID:Hyperbaric oxygen and aerobic exercise in the long-term treatment of fibromyalgia: A narrative review. 3039


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