Increased Glutamate/Glutamine Compounds in the Brains of Patients With Fibromyalgia A Magnetic Resonance Spectroscopy Study

Institut d'Investigacions Biomèdiques August Pi i Sunyer and Hospital Clínic of Barcelona, Barcelona, Spain.
Arthritis & Rheumatology (Impact Factor: 7.76). 06/2010; 62(6):1829-36. DOI: 10.1002/art.27430
Source: PubMed


Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques.
A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women.
In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean +/- SD 11.9 +/- 1.6 arbitrary units [AU] versus 13.4 +/- 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean +/- SD 2.1 +/- 0.4 versus 2.4 +/- 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher.
The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

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Available from: Nuria Bargalló, Oct 13, 2014
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    • "These structures include the primary and secondary sensory and motor cortices, insula, anterior cingulate cortex, thalamus, dorsolateral prefrontal cortex and basal ganglia - regions that have been named the ‘pain matrix’ because they are activated in response to a painful stimulus. A growing body of evidence suggests that glutamate (Glu), an excitatory neurotransmitter in the central nervous system, may play a part in the pathophysiology of FM, given that its concentration is elevated in the insula [8], hippocampus [9] and posterior cingulate cortex [10,11]. "
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    ABSTRACT: Fibromyalgia is a prevalent chronic rheumatic disease of great clinical importance. Recent studies have found raised levels of glutamate in the insula, hippocampus and posterior cingulate cortex regions of the brains of fibromyalgia (FM) patients. This finding has led researchers to speculate about the usefulness of glutamate-blocking drugs such as memantine in the treatment of fibromyalgia. The hypothesis of this study is that the administration of memantine will reduce the glutamate levels, and futhermore, will decrease the perceived pain. The aim of this study is to evaluate the efficacy of memantine in the treatment of pain (pain perception). A secondary objective is to evaluate the efficacy of memantine in the treatment of other clinical symptoms of FM, and to evaluate the efficacy of memantine in reducing brain levels of glutamate, and its effects on the central nervous system as a whole. A double-blind parallel randomized controlled trial. Participants, Seventy patients diagnosed with FM will be recruited from primary health care centers in Zaragoza, Spain. Intervention. The subjects will be randomized in two groups: A) A treatment group (n = 35), which will receive 20 mg of memantine daily; B) A control group (n = 35), to which will be administered a placebo. There will be a six-month follow-up period (including a titration period of one month). Outcomes. The main efficacy variable of this study is pain (pain perception). The secondary efficacy variables are clinical symptoms (pain threshold, cognitive function, health status, anxiety, depression, clinical impression and quality of life) and glutamate levels in different regions of the brain, which will be assessed by magnetic resonance spectroscopy. Randomization and blinding. Randomization has been computer-generated, and the random allocation sequence will be implemented by telephone. Subjects of the study and the research assistants will be blinded to group assignment. There is a need for the development of innovative and more effective treatments for fibromyalgia. This clinical trial will determine whether memantine can be an effective pharmacological treatment for fibromyalgia patients. Trial registration Current Controlled Trials http://ISRCTN45127327 EUDRACT 2011-006244-73
    Trials 01/2013; 14(1):3. DOI:10.1186/1745-6215-14-3 · 1.73 Impact Factor
    • "Thus it appears that there are multiple loci within the FM brain wherein elevations in Glx occur. This effect does not appear to be global or " non-specific " as elevated Glx levels are not detected in the anterior insula [18] or the prefrontal cortex [41] "
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    ABSTRACT: Proton magnetic resonance spectroscopy has been used extensively in the study of various neurobiological disorders: depression, schizophrenia, autism, etc. But its application to chronic pain is relatively new. Not many studies in chronic pain have used (1)H-MRS. The unique ability of (1)H-MRS to assess both static and dynamic levels of glutamate and γ-aminobutyric acid (GABA) gives this method a unique position in neuroscience. Emerging evidence in chronic pain suggests an elevated excitatory/inhibitory neurotransmitter ratio is present within brain regions involved in pain processing. The combination of (1)H-MRS imaging with pharmacologic interventions holds significant promise as a direct one-to-one matching of disease pathology with drug mechanism of action can be made. As such (1)H-MRS may be useful in discovery of novel compounds for chronic pain. Research in these areas may lead to improved diagnosis and treatment of these complex patients.
    Neuroscience Letters 03/2012; 520(2):192-6. DOI:10.1016/j.neulet.2012.03.042 · 2.03 Impact Factor
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    • "Another group used magnetic resonance spectroscopy techniques to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women. Patients with fibromyalgia showed higher levels of glutamate compounds in the right amygdala than did healthy controls, and pain was related to increased glutamate levels in the left thalamus (Valdés et al., 2010). These findings have implications for future therapies directed against glutamate receptors, but further studies are desirable to confirm whether these findings are observed in other functional pain syndromes. "

    New Insights into Fibromyalgia, 01/2012; , ISBN: 978-953-307-407-8
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