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)

The aims of the present study were to examine serotonergic markers, i.e. [3H]paroxetine binding characteristics and the availability of plasma tryptophan, the precursor of serotonin (5-HT), and the plasma concentrations of the branched chain amino acids (BCAAs), valine, leucine and isoleucine, in fibromyalgia. The [3H]paroxetine binding characteristics, B(max) and K(d) values, and tryptophan and the competing amino acids (CAA), known to compete for the same cerebral uptake mechanism (i.e. valine, leucine, isoleucine, phenylalanine and tyrosine), were determined in fibromyalgia patients and normal controls. There were no significant differences in the [3H]paroxetine binding characteristics (B(max) and K(d)) between fibromyalgia and control subjects. There were no significant differences in plasma tryptophan or the tryptophan/CAA ratio between fibromyalgia patients and normal controls. In the fibromyalgia patients, there were no significant correlations between [3H]paroxetine binding characteristics or the availability of tryptophan and myalgic or depressive symptoms. Patients with fibromyalgia had significantly lower plasma concentrations of the three BCAAs (valine, leucine and isoleucine) and phenylalanine than normal controls. It is hypothesized that the relative deficiency in the BCAAs may play a role in the pathophysiology of fibromyalgia, since the BCAAs supply energy to the muscle and regulate protein synthesis in the muscles. A supplemental trial with BCAAs in fibromyalgia appears to be justified.
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PMID:Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia. 1110 53

Fibromyalgia is a form of non-articular rheumatism characterised by long term (>3 months) and widespread musculoskeletal aching, stiffness and pressure hyperalgesia at characteristic soft tissue sites, called soft tissue tender points. The biophysiology of fibromyalgia, however, has remained elusive and the treatment remains mainly empirical. This article reviews the neuroendocrine-immune pathophysiology of fibromyalgia. There is no major evidence that fibromyalgia is accompanied by activation of the inflammatory response system, by immune activation or by an inflammatory process. There is some evidence that fibromyalgia is accompanied by some signs of immunosuppression, suggesting that immunomodifying drugs could have potential in the treatment of fibromyalgia. Recent trials with cytokines, such as interferon-alpha, have been undertaken in patients with fibromyalgia. Immunotherapy with these agents, however, may induce symptoms reminiscent of fibromyalgia and depression in a considerable number of patients. Lowered serum activity of prolyl endopeptidase (PEP), a cytosolic endopeptidase that cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass, may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides, e.g. substance P. Trials with PEP agonists could be worthwhile in fibromyalgia. The muscle energy depletion hypothesis of fibromyalgia is supported by findings that this condition is accompanied by lowered plasma levels of branched chain amino acids (BCAAs), i.e. valine, leucine and isoleucine. Since there is evidence that BCAA supplementation decreases muscle catabolism and has ergogenic values, a supplemental trial with BCAAs in fibromyalgia appears to be justified.
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PMID:Neuroendocrine and immune aspects of fibromyalgia. 1154 93

Pregabalin (PGB) is a novel drug under development for the treatment of epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. In this study, we investigated PGB transport in rats, mammalian cell lines, and Xenopus laevis oocytes. In contrast to gabapentin (GBP), PGB absorption in rats showed unique linear pharmacokinetics. PGB entered CHO and Caco-2 cells predominately via Na(+)-independent processes. Uptake of PGB was mutually exclusive with leucine, GBP and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, the substrates preferential for system L. The preloaded PGB in CHO cells was exchangeable with leucine, but at a lower exchange rate than that of leucine and GBP. Dixon plots showed competitive inhibition of leucine uptake by PGB, with a K(i) value very close to the K(m) value for PGB uptake (377 versus 363 microM). At an extracellular concentration of 300 microM, the intracellular PGB concentration in CHO cells reached 1.5- and 23-fold higher than that of GBP and leucine, respectively. In contrast, at clinically relevant concentrations, PGB seemed not to interact with GABA transport in GAT1, GAT2, and GAT3 cell lines, system y(+), b(0,+), B(0,+), and B(0) transport activities in Caco-2 and NBL-1 cells, and the b(0,+)-like transport activity in rBAT cRNA-injected X. laevis oocytes. Taken together, these results suggest that L-type transport is the major transport route for PGB and GBP uptake in mammalian cells. The differential affinity of PGB and GBP at L-type system leads to more concentrative accumulation of PGB than GBP, which may facilitate PGB transmembrane absorption in vivo.
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PMID:Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. 1576 62

The objectives of our study were to evaluate free amino acid (FAA) concentrations in the serum of patients affected by fibromyalgia syndrome (FMS) and to determine the relationships between FAA levels and FMS clinical parameters. Thus, serum amino acid concentrations were quantified (HPLC analysis) in 23 females with fibromyalgia (according to the American College of Rheumatology classification criteria) and 20 healthy females. The results showed significantly higher serum concentrations of aspartate, cysteine, glutamate, glycine, isoleucine, leucine, methionine, ornithine, phenylalanine, sarcosine, serine, taurine, tyrosine and valine in FMS patients vs. healthy controls. Patients with higher Fibromyalgia Impact Questionnaire (FIQ) scores showed increased levels of alanine, glutamine, isoleucine, leucine, phenylalanine, proline and valine. In conclusion, our results indicate an imbalance in some FAAs in FMS patients. Increased Glu is particularly interesting, as it could explain the deficit in monoaminergic transmission involved in pain.
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PMID:Free amino acids in fibromyalgia syndrome: relationship with clinical picture. 2807 4