Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Abstract

Objective. 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.Methods. 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.Results. 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.Conclusion. 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. Fibromyalgia (FM) is a clinical syndrome definedby the presence of chronic widespread musculoskeletal pain and the presence of at least 11 of 18 body tender points that are representative of a possible enhanced sensitivity to painful stimulation (1), and these features are often accompanied by other symptoms such as fatigue, poor sleep quality, loss of memory, and mood disturbances. The lack of clear evidence of peripheral tissue damage to which such symptoms could be attributed (2) and the findings of peculiar abnormalities in both the neural pain modulation pattern (3,4) and the hypothalamic-pituitary-adrenal axis (5) in these patients have contributed to the current understanding of FM as a central sensitization syndrome of unknown origin. In our conceptual framework, FM symptoms are related to neural and psychological abnormalities in sensory and emotional processing that result from biologic (genetic) predispositions, early adverse experiences (emotional neglect, physical or sexual abuse, family dysfunction), psychological vulnerabilities (neuroticism, negative affect, social learning), and biographically related precipitating factors (physical or psychosocial stress) (6,7).In the last decade, the important progress made in neuroimaging techniques has enabled the study of several aspects of cerebral pain processing. Research on Supported by the Ministerio de Sanidad y Consumo, Spain (grant FIS PI 04/1077).

Metabolic Abnormalities in Pain-Processing Regions of Patients with Fibromyalgia: A 3T MR Spectroscopy Study

“…[10][11][12][13] Although there were no differences between patients and controls at this level, we found a strong significant positive correlation between Glu/Cr levels in the left thalamus and the VAS (r ϭ 0.730, P ϭ .007). This result strengthens a recently published MRS study, 26 in which patients with more pain (high VAS score) showed higher Glx levels in the left thalamus, though without significant correlation. Our result could reflect the role of the thalamic structures in the processing of pain signal intensity.…”

“…Our result could reflect the role of the thalamic structures in the processing of pain signal intensity. However, both in our study and in the previous MRS studies 26,27 that explored this region, no differences between patients and HC were found in metabolites and their ratios, even though alterations of CBF are well documented at this level. In our opinion, this information suggests that the thalamus is not primarily involved in this disorder but probably interacts with other cognitive areas that process pain such as the VLPFC.…”

“…Although the results of these studies are not homogeneous, [21][22][23][24][25][26][27] because of the different MRS protocols, magnetic fields used, and areas of study, in 4 of these, alterations of the glutamatergic system were detected.…”

“…Recently, some MRS studies [21][22][23][24][25][26][27] have demonstrated alteration of cerebral metabolites in patients with FM, and though the results are not homogeneous, they strengthen the hypothesis of a neural dysfunction secondary to the pain processing.…”

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

“…Human MRS studies have identified increased inositol in medial temporal lobe including amygdala (Venkatraman et al, 2009) and in fronto-cortical (PFC, ACC) gray and white matter (Caetano et al, 2005;Kumar et al, 2002) in depression, and in amygdala and thalamus in association with high depression symptoms in fibromyalgia (Valdes et al, 2010); decreased PFC-ACC inositol has also been reported in depression (Coupland et al, 2005). Inositol is an intracellular lipid and precursor of phosphatidylinositol (PI) structural lipids and inositol phosphate secondary messengers e.g.…”