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European Radiology
Published in: European Radiology 2/2013

01-02-2013 | Magnetic Resonance

Differential NMR spectroscopy reactions of anterior/posterior and right/left insular subdivisions due to acute dental pain

Authors: Andreas Gutzeit, Dieter Meier, Johannes M. Froehlich, Klaus Hergan, Sebastian Kos, Constantin v. Weymarn, Kai Lutz, Dominik Ettlin, Christoph A. Binkert, Jochen Mutschler, Sabine Sartoretti-Schefer, Mike Brügger

Published in: European Radiology | Issue 2/2013

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Abstract

Objectives

The insular cortex has an important role within the cerebral pain circuitry. The aim of this study was to measure metabolic alterations by MR spectroscopy due to experimentally induced trigeminal pain in the anterior/posterior and right/left insular subdivisions.

Methods

Sixteen male volunteers were investigated using magnetic resonance (MR) spectroscopy before, during and after experimentally induced dental pain. Biphasic bipolar electric current pulses of 1 ms duration were administered based on the subjectively determined pain threshold. Volunteers were instructed to rate every stimulus using a MR compatible rating scale.

Results

Due to the pain stimulation a significant absolute increase in glutamate (Glu, F = 6.1; P = 0.001), glutamine (Gln, F = 11.2; P = 0.001) as well as glutamate/glutamine (Glx, F = 17.7; P = 0.001) were observed, whereas myo-inositol (mI, F = 9.5;P = 0.001) showed a significant drop. Additionally, these metabolites showed a significant effect towards lateralisation, meaning that metabolic concentration differed either in left or right insular subdivision. Creatine demonstrated also an absolute significant decrease during stimulation (F = 2.8; P = 0.022) with a significant anterior-posterior difference (F = 40.7; P = 0.001).

Conclusions

Results confirm that the insular cortex is a metabolically high active region in pain processing within the brain. Quantitative metabolic changes show that there is a distinct but locally diverse neurometabolic activity under acute pain. The known cytoarchitectonic subdivisions show different metabolic reactions and give new insights into pain-processing physiology.

Key Points

• Dental pain leads to recognisable changes in MR spectroscopy of the insula
• Immediate changes in glutamate, glutamine, composite glutamine/glutamate and myo-inositol are seen
• Sub-regions demonstrate different metabolic reaction patterns to acute trigeminal pain stimulation
• Differing metabolic reaction patterns to acute trigeminal pain stimulation confirm cytoarchitectonic differentiation
Appendix
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Literature
1.
2.
Legrain V, Iannetti GD, Plaghki L, Mouraux A (2011) The pain matrix reloaded: a salience detection system for the body. Prog Neurobiol 93:111–124PubMedCrossRef
3.
Apkarian AV, Bushnell MC, Treede RD, Zubieta JK (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9:463–484PubMedCrossRef
4.
Peyron R, García-Larrea L, Grégoire MC et al (2000) Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case. Pain 84:77–87PubMedCrossRef
5.
Peyron R, Laurent B, García-Larrea L (2000) Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin 30:263–288PubMedCrossRef
6.
Brooks JC, Nurmikko TJ, Bimson WE, Singh KD, Roberts N (2002) fMRI of thermal pain: effects of stimulus laterality and attention. NeuroImage 15:293–301PubMedCrossRef
7.
8.
Friebel U, Eickhoff SB, Lotze M (2011) Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain. NeuroImage 58:1070–1080PubMedCrossRef
9.
Vogt BA (2005) Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 6:533–544PubMedCrossRef
10.
Kurth F, Zilles K, Fox PT, Laird AR, Eickhoff SB (2010) A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis. Brain Struct Funct 214:519–534PubMedCrossRef
11.
Mazzola L, Isnard J, Peyron R, Mauguière F (2012) Stimulation of the human cortex and the experience of pain: Wilder Penfield’s observations revisited. Brain 135:631–640PubMedCrossRef
12.
Varnavas GG, Grand W (1999) The insular cortex: morphological and vascular anatomic characteristics. Neurosurgery 44:127–136PubMedCrossRef
13.
Brodmann K (1909) Vergleichende Lokalisationslehre der Grosshirnrinde in Ihren Prinzipien dargestellt aufgrund des Zellenbaues. Barth J.A, Leipzig
14.
Kurth F, Eickhoff SB, Schleicher A, Hoemke L, Zilles K, Amunts K (2010) Cytoarchitecture and probabilistic maps of the human posterior insular cortex. Cereb Cortex 20:1448–1461PubMedCrossRef
15.
Baumgärtner U, Tiede W, Treede RD, Craig AD (2006) Laser-evoked potentials are graded and somatotopically organized anteroposteriorly in the operculoinsular cortex of anesthetized monkeys. J Neurophysiol 96:2802–2808PubMedCrossRef
16.
Craig AD, Chen K, Bandy D, Reiman EM (2000) Thermosensory activation of insular cortex. Nat Neurosci 3:184–190PubMedCrossRef
17.
Bamiou DE, Musiek FE, Luxon LM (2003) The insula (Island of Reil) and its role in auditory processing. Literature review. Brain Res Brain Res Rev 42:143–154PubMedCrossRef
18.
Baliki MN, Geha PY, Apkarian AV (2009) Parsing pain perception between nociceptive representation and magnitude estimation. J Neurophysiol 101:875–887PubMedCrossRef
19.
Seeley WW (2010) Anterior insula degeneration in frontotemporal dementia. Brain Struct Funct 214:465–475PubMedCrossRef
20.
21.
Barker PB, Lin DDM (2006) In vivo proton MR spectroscopy of the human brain. Prog Nucl Magn Reson Spectrosc 49:99–128CrossRef
22.
Grachev ID, Fredrickson BE, Apkarian AV (2000) Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study. Pain 89:7–18PubMedCrossRef
23.
Siddall PJ, Stanwell P, Woodhouse A et al (2006) Magnetic resonance spectroscopy detects biochemical changes in the brain associated with chronic low back pain: a preliminary report. Anesth Analg 102:1164–1168PubMedCrossRef
24.
Kupers R, Danielsen ER, Kehlet H, Christensen R, Thomsen C (2009) Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man. Pain 142:89–93PubMedCrossRef
25.
Gutzeit A, Meier D, Meier ML et al (2011) Insula-specific responses induced by dental pain. A proton magnetic resonance spectroscopy study. Eur Radiol 21:807–815PubMedCrossRef
26.
27.
Keller T, Popovic MR, Pappas IP, Müller PY (2002) Transcutaneous functional electrical stimulator “Compex Motion”. Artif Organs 26:219–223PubMedCrossRef
28.
Dunckley P, Wise RG, Aziz Q et al (2005) Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness. Neuroscience 133:533–542PubMedCrossRef
29.
Iannetti GD, Zambreanu L, Wise RG et al (2005) Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Proc Natl Acad Sci USA 102:18195–18200PubMedCrossRef
30.
31.
Baumgärtner U, Iannetti GD, Zambreanu L, Stoeter P, Treede RD, Tracey I (2010) Multiple somatotopic representations of heat and mechanical pain in the operculo-insular cortex: a high-resolution fMRI study. J Neurophysiol 104:2863–2872PubMedCrossRef
32.
Mazzola L, Isnard J, Peyron R, Guénot M, Mauguière F (2009) Somatotopic organization of pain responses to direct electrical stimulation of the human insular cortex. Pain 146:99–104PubMedCrossRef
33.
Brooks JC, Zambreanu L, Godinez A, Craig AD, Tracey I (2005) Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging. NeuroImage 27:201–209PubMedCrossRef
34.
Gussew A, Rzanny R, Güllmar D, Scholle HC, Reichenbach JR (2011) 1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain. NeuroImage 54:1315–1323PubMedCrossRef
35.
Gussew A, Rzanny R, Erdtel M et al (2010) Time-resolved functional 1H MR spectroscopic detection of glutamate concentration changes in the brain during acute heat pain stimulation. NeuroImage 49:1895–1902PubMedCrossRef
36.
Petrou M, Harris RE, Foerster BR et al (2008) Proton MR spectroscopy in the evaluation of cerebral metabolism in patients with fibromyalgia: comparison with healthy controls and correlation with symptom severity. AJNR Am J Roentgenol 29:913–918
37.
Gustin SM, Peck CC, Wilcox SL, Nash PG, Murray GM, Henderson LA (2011) Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes. J Neurosci 31:5956–5964PubMedCrossRef
38.
Harris RE, Sundgren PC, Craig AD et al (2009) Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum 60:3146–3152PubMedCrossRef
39.
Valdés M, Collado A, Bargalló N et al (2010) Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: a magnetic resonance spectroscopy study. Arthritis Rheum 62:1829–1836PubMedCrossRef
40.
Fayed N, Garcia-Campayo J, Magallón R et al (2010) Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate. Arthritis Res Ther 12:R134PubMedCrossRef
41.
Teutsch S, Herken W, Bingel U, Schoell E, May A (2008) Changes in brain gray matter due to repetitive painful stimulation. NeuroImage 42:845–849PubMedCrossRef
42.
43.
Mullins PG, Rowland LM, Jung RE, Sibbitt WL Jr (2005) A novel technique to study the brain’s response to pain: proton magnetic resonance spectroscopy. NeuroImage 26:642–646PubMedCrossRef
44.
Craig AD (2003) Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 13:500–505PubMedCrossRef
45.
Lamm C, Singer T (2010) The role of anterior insular cortex in social emotions. Brain Struct Funct 214:579–591PubMedCrossRef
46.
47.
Phillips ML, Drevets WC, Rauch SL, Lane R (2003) Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 54:504–514PubMedCrossRef
48.
49.
Brügger M, Ettlin DA, Meier M et al (2011) Taking sides with pain—lateralization aspects related to cerebral processing of dental pain. Front Hum Neurosci 5:12PubMedCrossRef
50.
Brügger M, Lutz K, Brönnimann B et al (2012) Tracing toothache intensity in the brain. J Dent Res 91:156–160PubMedCrossRef
51.
Pouwels PJ, Frahm J (1998) Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med 39:53–60PubMedCrossRef
52.
Christiansen P, Toft P, Larsson HB, Stubgaard M, Henriksen O (1993) The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium. Magn Reson Imaging 11:799–806PubMedCrossRef
53.
Komoroski RA, Kotrla KJ, Lemen L, Lindquist D, Diaz P, Foundas A (2004) Brain metabolite concentration ratios in vivo: multisite reproducibility by single-voxel 1H MR spectroscopy. Magn Reson Imaging 22:721–725PubMedCrossRef
Metadata
Title
Differential NMR spectroscopy reactions of anterior/posterior and right/left insular subdivisions due to acute dental pain
Authors
Andreas Gutzeit
Dieter Meier
Johannes M. Froehlich
Klaus Hergan
Sebastian Kos
Constantin v. Weymarn
Kai Lutz
Dominik Ettlin
Christoph A. Binkert
Jochen Mutschler
Sabine Sartoretti-Schefer
Mike Brügger
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
European Radiology / Issue 2/2013
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-012-2621-0

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