Insula-specific responses induced by dental pain. A proton magnetic resonance spectroscopy study

ObjectivesTo evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate.MethodsTen male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87–92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy.ResultsSignificant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (−9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate.ConclusionThe insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed.

[1]  Hans-Joachim Mentzel,et al.  Time-resolved functional 1H MR spectroscopic detection of glutamate concentration changes in the brain during acute heat pain stimulation , 2010, NeuroImage.

[2]  Ron Kupers,et al.  Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man , 2009, Pain.

[3]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[4]  Toshiro Inubushi,et al.  N-Acetylaspartate concentrations in the thalami of neuropathic pain patients and healthy comparison subjects measured with (1)H-MRS. , 2006, Magnetic resonance imaging.

[5]  Z. Wiesenfeld‐Hallin,et al.  Sex differences in pain perception. , 2005, Gender medicine.

[6]  Steven Laureys,et al.  Perception of pain in the minimally conscious state with PET activation: an observational study , 2008, The Lancet Neurology.

[7]  F. Mauguière,et al.  Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case , 2000, Pain.

[8]  Douglas L Rothman,et al.  Magnetic resonance spectroscopy of neurotransmitters in human brain , 2003, Annals of neurology.

[9]  J. Maisog,et al.  Pain intensity processing within the human brain: a bilateral, distributed mechanism. , 1999, Journal of neurophysiology.

[10]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[11]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[12]  Eszter D. Schoell,et al.  Changes in brain gray matter due to repetitive painful stimulation , 2008, NeuroImage.

[13]  J. Dostrovsky,et al.  Pain-related neurons in the human cingulate cortex , 1999, Nature Neuroscience.

[14]  S. Bluml,et al.  Magnetic resonance spectroscopy of the human brain , 2001, The Anatomical record.

[15]  J C Gore,et al.  Functional MR imaging of regional brain activation associated with the affective experience of pain. , 2001, AJR. American journal of roentgenology.

[16]  Rex E. Jung,et al.  A novel technique to study the brain's response to pain: Proton magnetic resonance spectroscopy , 2005, NeuroImage.

[17]  H. Handwerker,et al.  Cortical representation of experimental tooth pain in humans , 2005, Pain.

[18]  Claudio Babiloni,et al.  Human secondary somatosensory cortex is involved in the processing of somatosensory rare stimuli: An fMRI study , 2008, NeuroImage.

[19]  P. Magistretti,et al.  Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[20]  Richard E. Harris,et al.  Proton MR Spectroscopy in the Evaluation of Cerebral Metabolism in Patients with Fibromyalgia: Comparison with Healthy Controls and Correlation with Symptom Severity , 2008, American Journal of Neuroradiology.

[21]  Ronald Melzack,et al.  From the gate to the neuromatrix , 1999, Pain.

[22]  Silvia Mangia,et al.  Metabolic and Hemodynamic Events after Changes in Neuronal Activity: Current Hypotheses, Theoretical Predictions and in vivo NMR Experimental Findings , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  Ravi S. Menon,et al.  Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. , 2002, The American journal of psychiatry.

[24]  W Vennart,et al.  Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Lumy Sawaki,et al.  Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions , 2009, The Journal of Neuroscience.

[26]  J. Luciano,et al.  Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate , 2010, Arthritis research & therapy.

[27]  E L FOLTZ,et al.  Pain "relief" by frontal cingulumotomy. , 1962, Journal of neurosurgery.

[28]  A. May.  Chronic pain may change the structure of the brain , 2008, PAIN®.

[29]  W. Richter,et al.  Distraction Modulates Anterior Cingulate Gyrus Activations during the Cold Pressor Test , 2001, NeuroImage.

[30]  C. Sorg,et al.  Patients With Pain Disorder Show Gray-Matter Loss in Pain-Processing Structures: A Voxel-Based Morphometric Study , 2009, Psychosomatic medicine.

[31]  G Rager,et al.  Gross anatomy in the surgical curriculum in Switzerland: Improved cadaver preservation, anatomical models, and course development , 2001, The Anatomical record.

[32]  Angela R Laird,et al.  Brain activity associated with painfully hot stimuli applied to the upper limb: A meta‐analysis , 2005, Human brain mapping.

[33]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[34]  J. Lauriello,et al.  Proton magnetic resonance spectroscopy (H-MRS) studies of schizophrenia. , 2001, Seminars in clinical neuropsychiatry.

[35]  A. Vania Apkarian,et al.  Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study , 2000, Pain.

[36]  Jonathan C. W. Brooks,et al.  Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging , 2005, NeuroImage.

[37]  A. Wunderlich,et al.  Perception and suppression of thermally induced pain: A fMRI study , 2009, Somatosensory & motor research.

[38]  T. Keller,et al.  Interindividual differences in the perception of dental stimulation and related brain activity. , 2009, European journal of oral sciences.

[39]  Milos R Popovic,et al.  Transcutaneous functional electrical stimulator "Compex Motion". , 2002, Artificial organs.

[40]  Uwe Himmelreich,et al.  Magnetic Resonance Spectroscopy Detects Biochemical Changes in the Brain Associated with Chronic Low Back Pain: A Preliminary Report , 2006, Anesthesia and analgesia.

[41]  Qasim Aziz,et al.  A Comparison of Visceral and Somatic Pain Processing in the Human Brainstem Using Functional Magnetic Resonance Imaging , 2005, The Journal of Neuroscience.