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)

Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.
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PMID:Is insulin resistance the cause of fibromyalgia? A preliminary report. 3179 Apr 94

Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).
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PMID:Metformin: A Prospective Alternative for the Treatment of Chronic Pain. 3317 15

The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
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PMID:Coenzyme Q10: Novel Formulations and Medical Trends. 3318 46


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