Elevated insular glutamate in fibromyalgia is associated with experimental pain

Abstract

Objective. Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report.Methods. Nineteen FM patients and 14 age-and sex-matched pain-free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session in which the right anterior insula and right posterior insula were examined at rest.Results. Compared with healthy controls, FM patients had significantly higher levels of Glu (mean ؎ SD 8.09 ؎ 0.72 arbitrary institutional units versus 6.86 ؎ 1.29 arbitrary institutional units; P ‫؍‬ 0.009) and combined glutamine and Glu (i.e., Glx) (mean ؎ SD 12.38 ؎ 0.94 arbitrary institutional units versus 10.59 ؎ 1.48 arbitrary institutional units; P ‫؍‬ 0.001) within the right posterior insula. No significant differences between groups were detected in any of the other major metabolites within this region (P > 0.05 for all comparisons), and no group differences were detected for any metabolite within the right anterior insula (P > 0.11 for all comparisons). Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure pain thresholds across both groups for medium pain (for Glu, r ‫؍‬ ؊0.43, P ‫؍‬ 0.012; for Glx, r ‫؍‬ ؊0.50, P ‫؍‬ 0.003).Conclusion. Enhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes.

Pressure Pain Sensitivity and Insular Combined Glutamate and Glutamine (Glx) Are Associated with Subsequent Clinical Response to Sham But Not Traditional Acupuncture in Patients Who Have Chronic Pain

“…12,13 Interestingly, the current authors' group demonstrated that the degree of enhanced pain sensitivity in FM is associated with elevated levels of combined glutamate (Glu), an excitatory neurotransmitter, and glutamine (Gln; combination, Glx) within the insula, a brain region involved in higher-order sensory processing. 14,15 These data have led the current authors and other researchers to speculate that elevated excitatory neurotransmission may play a role in enhanced pain sensitivity in FM. However, the role of this enhanced sensitivity in treatment response has largely been unexplored.…”

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

“…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.…”

Augmented central pain processing in vulvodynia

“…23,21 Findings of generalized hyperalgesia (an increased response to painful stimuli) and allodynia (painful response to a non-painful stimuli) are also present in fibromyalgia. 14,17 We hypothesized that the enhanced brain response seen in women with FM compared to HCs in pain related regions such as the insula cortex, somatosensory, dorsolateral prefrontal cortex, thalamus and cingulate cortex, 17,9 may also be present in individuals with VVD, if these two pain conditions have similar pathobiology, as suggested by the observed generalized hyperalgesia.…”