A novel technique to study the brain's response to pain: Proton magnetic resonance spectroscopy

Mullins, Paul G.; Rowland, Laura M.; Jung, Rex E.; Sibbitt, Wilmer L.

doi:10.1016/j.neuroimage.2005.02.001

Cited by 114 publications

(100 citation statements)

References 26 publications

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“…Since Glu is a major excitatory neurotransmitter involved in pain transmission, these observations are not unexpected. Our data are also consistent with findings from a recent H-MRS study in which increases in Glu/Cr within the anterior cingulate were observed in response to cold pain in healthy pain-free controls (14). However, the present data show primarily the converse of this relationship, namely, reductions in pain in association with lower Glu/Cr values.…”

Section: Discussionsupporting

confidence: 93%

“…Since detecting Glu-specific concentrations accurately at 3T in humans is difficult because of the overlapping proton resonances between Gln and Glu, we also investigated the combinations of Glu/Cr and Gln/Cr (i.e., Glx/Cr), which may be less controversial (14). Similar to the above-described results, we found that pre-to posttreatment changes in Glx/Cr within the insula were negatively correlated with pre-to posttreatment changes in pressure-evoked pain thresholds.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

Harris¹,

Sundgren²,

Pang³

et al. 2008

Arthritis & Rheumatism

182

159

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Objective. Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM.Methods. Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Fibromyalgia (FM) is a chronic widespread pain disorder that affects ϳ2-4% of individuals in industrialized countries (1). Although the underlying etiology of this condition is unknown, dysfunction within the central nervous system has been implicated. Results from functional magnetic resonance imaging (FMRI) (2,3), singlephoton emission tomography (4), and positron emission tomography (5) support this hypothesis.One structure that is consistently found to be associated with augmented evoked pain activity in FM is the insula (2,3). In addition to its function in speech, taste, and auditory systems, the insula is also intimately involved in somatosensory and visceral pain processing (6). It is strategically located in a bidirectional pathway between the secondary somatosensory cortex and the amygdala (6). This anatomic position may give the insula ClinicalTrials.gov identifier: NCT00142597.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

Harris¹,

Sundgren²,

Pang³

et al. 2008

Arthritis & Rheumatism

182

159

View full text Add to dashboard Cite

show abstract

“…30 There are many studies on the implication of Glu in nociception. [31][32][33] In particular, an increase of Glu at the level of anterior cingulate cortex was demonstrated by Mullins et al 34 in association with painful stimuli, and these variations correlated with the perceived pain intensity. Our results confirm this glutamatergic alteration, and the increase of Glx/Cr and Glu/Cr in both VLPFCs and not in thalami adds new insight into the physiopathology.…”

Section: Discussionmentioning

confidence: 88%

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

Feraco¹,

Bacci²,

Pedrabissi³

et al. 2011

AJNR Am J Neuroradiol

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“…Dynamic 1H-MRS studies in normal human volunteers have similarly found local activity-dependent increases in cortical glutamate. Mullins et al (2005) observed a 9% increase in glutamate in the anterior cingulate cortex during cold pressor pain. Gussaw et al (2010) subsequently showed an 18% increase in anterior insular cortex glutamate during thermal pain.…”

Section: Glutamate and Glutaminementioning

confidence: 89%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Brain Imaging in Behavioral Neuroscience

219

194

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The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics,and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate(NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action,and allow clinical monitoring of the effects of interventions on brain metabolicmarkers

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A novel technique to study the brain's response to pain: Proton magnetic resonance spectroscopy

Cited by 114 publications

References 26 publications

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

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

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

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