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)

Considerable evidence has accrued in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system occur in patients with major depression. These findings include the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT) in drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased plasma tryptophan concentrations in depressed patients and a profound relapse in remitted depressed patients who have responded to a serotonergic antidepressant when brain tryptophan availability is reduced; (d) in general, all clinically efficacious antidepressants augment 5-HT neurotransmission following chronic treatment; (e) clinically efficacious antidepressant action by all inhibitors of 5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem brain tissue of depressed patients and suicide victims, as well as in platelets of drug-free depressed patients; (g) decreased number of 5-HT transporter (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem brain tissue of suicide victims and depressed patients and in platelets of drug-free depressed patients. In our studies, this reduction in platelet 5-HT transporter binding is not due to prior antidepressant treatment of hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia, panic disorder, fibromyalgia, or atypical depression. In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.
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PMID:Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. 1949 50

The serotonergic system has repeatedly been discussed to be involved in the pathophysiology of fibromyalgia (FM), which is a syndrome of widespread pain and sleep disturbance. Elevated levels of substance P (SP), a mediator of nociception, have been described in FM. In this study the possible relationship between SP and serotonin (5-HT) together with its precursor tryptophan (TRP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was evaluated in 51 serum samples of fibromyalgia patients. These parameters were compared with clinical data such as pain intensity or sleep quality. A strong negative correlation between SP and 5-HIAA (P = .000) as well as between SP and TRP (P = .009) could be demonstrated. High serum concentrations of 5-HIAA and TRP showed a significant relation to low pain scores (5-HIAA: P = .030; TRP: P = .014). Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia.
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PMID:Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients. 1002 91

Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesized underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.
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PMID:Evidence for an altered tryptophan metabolism in fibromyalgia. 1258 52

Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesised underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and Interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism and IL-6 production. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.
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PMID:Experimental evaluation of an altered tryptophan metabolism in fibromyalgia. 1520 40

Fibromyalgia (FM) is a chronic complex musculoskeletal disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep disturbance, memory defects and mood changes. Fisetin, a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. The present study aimed to evaluate the efficacy of fisetin against reserpine-induced FM (RIF) in rats. RIF was induced in male Wistar rats (180-220 gm) using reserpine (1 mg/kg; subcutaneous; once daily for 3 consecutive days) and the rats were treated with fisetin (5, 10 and 25 mg/kg) for 21 days. Various behavioral, biochemical and molecular parameters were evaluated. Administration of reserpine induced allodynia, hyperalgesia and depression, which were significantly ameliorated (P<0.05) by fisetin (10 and 25 mg/kg), as reflected by an increase in paw and tail withdrawal latency, increased paw withdrawal threshold, and decreased immobility time. Reserpine led to decreased biogenic amine levels [5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA)] and increased the ratio to their metabolite 3,4-dihydroxyphenylacetic acid. 5-hydroxyindoleacetic acid in the spinal cord, thalamus and prefrontal cortex was significantly decreased (P<0.05) by fisetin. Immunohistological analysis of brain tissue revealed that fisetin significantly inhibited (P<0.05) reserpine-induced depletion of 5-HT. It also significantly inhibited (P<0.05) elevated oxido-nitrosative stress and reactive oxygen species (ROS) levels, as analyzed by flow cytometry in RIF rats. Fisetin exerts its antinociceptive and anti-depressive potential via modulation of decreased levels of biogenic amines (5-HT, NA and DA), elevated oxido-nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental RIF.
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PMID:Attenuation of reserpine-induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol. 3201 Mar 8