Pain imaging in health and disease--how far have we come?

Since modern brain imaging of pain began 20 years ago, networks in the brain related to pain processing and those related to different types of pain modulation, including placebo, have been identified. Functional and anatomical connectivity of these circuits has begun to be analyzed. Imaging in patients suggests that chronic pain is associated with altered function and structural abnormalities in pain modulatory circuits. Moreover, biochemical alterations associated with chronic pain are being identified that provide information on cellular correlates as well as potential mechanisms of structural changes. Data from these brain imaging studies reinforce the idea that chronic pain leads to brain changes that could have functional significance.

[1]  Kirsten Tillisch,et al.  Regional gray matter density changes in brains of patients with irritable bowel syndrome. , 2010, Gastroenterology.

[2]  E. Holmes,et al.  Induction of Depressed Mood Disrupts Emotion Regulation Neurocircuitry and Enhances Pain Unpleasantness , 2010, Biological Psychiatry.

[3]  Jesús Pujol,et al.  Dynamic assessment of the right lateral frontal cortex response to painful stimulation , 2010, NeuroImage.

[4]  P. Schweinhardt,et al.  Supraspinal Pain Processing: Distinct Roles of Emotion and Attention , 2010, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[5]  P W Stroman,et al.  Tactile Sensory and Pain Networks in the Human Spinal Cord and Brain Stem Mapped by Means of Functional MR Imaging , 2010, American Journal of Neuroradiology.

[6]  I. Tracey,et al.  The pain matrix: Reloaded or reborn as we image tonic pain using arterial spin labelling , 2010, PAIN®.

[7]  Frank S. Prato,et al.  Using perfusion MRI to measure the dynamic changes in neural activation associated with tonic muscular pain , 2010, PAIN®.

[8]  Katja Wiech,et al.  Prestimulus functional connectivity determines pain perception in humans , 2009, Proceedings of the National Academy of Sciences.

[9]  Pierre Rainville,et al.  Cerebral and Cerebrospinal Processes Underlying Counterirritation Analgesia , 2009, The Journal of Neuroscience.

[10]  Arne May,et al.  Brain Gray Matter Decrease in Chronic Pain Is the Consequence and Not the Cause of Pain , 2009, The Journal of Neuroscience.

[11]  C. Ledbetter,et al.  Changes in Hippocampal Metabolites After Effective Treatment for Fibromyalgia: A Case Study , 2009, The Clinical journal of pain.

[12]  Christian Büchel,et al.  Direct Evidence for Spinal Cord Involvement in Placebo Analgesia , 2009, Science.

[13]  H. Diener,et al.  Gray matter changes related to chronic posttraumatic headache , 2009, Neurology.

[14]  A. Carr,et al.  Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. , 2009, Arthritis and rheumatism.

[15]  David A. Seminowicz,et al.  MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain , 2009, NeuroImage.

[16]  Irene Tracey,et al.  The influence of negative emotions on pain: Behavioral effects and neural mechanisms , 2009, NeuroImage.

[17]  Gian Domenico Iannetti,et al.  Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception , 2009, PAIN®.

[18]  C. Büchel,et al.  Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia , 2009, Neuron.

[19]  V. Jousmäki,et al.  Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain , 2009, PAIN®.

[20]  Steven C. R. Williams,et al.  Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain , 2009, PAIN®.

[21]  Jullie W Pan,et al.  Hippocampal correlates of pain in healthy elderly adults: A pilot study , 2009, Alzheimer's & Dementia.

[22]  B. Pfleiderer,et al.  Decreased Gray Matter Volumes in the Cingulo-Frontal Cortex and the Amygdala in Patients With Fibromyalgia , 2009, Psychosomatic medicine.

[23]  M. Glabus,et al.  Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism. , 2009, The journal of pain : official journal of the American Pain Society.

[24]  Serge Marchand,et al.  The Deficit of Pain Inhibition in Fibromyalgia Is More Pronounced in Patients With Comorbid Depressive Symptoms , 2009, The Clinical journal of pain.

[25]  M. Bushnell,et al.  Mood Influences Supraspinal Pain Processing Separately from Attention , 2009, The Journal of Neuroscience.

[26]  Fuqiang Zhao,et al.  Pain fMRI in rat cervical spinal cord: An echo planar imaging evaluation of sensitivity of BOLD and blood volume-weighted fMRI , 2009, NeuroImage.

[27]  David Borsook,et al.  Excitatory neurotransmitters in brain regions in interictal migraine patients , 2009, Molecular pain.

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

[29]  M. C. Bushnell,et al.  Increased gray matter density in young women with chronic vulvar pain , 2008, PAIN.

[30]  Maximilian Reiser,et al.  White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. , 2008, Arthritis and rheumatism.

[31]  Todd B. Parrish,et al.  The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions , 2008, Neuron.

[32]  L. Becerra,et al.  Interictal Dysfunction of a Brainstem Descending Modulatory Center in Migraine Patients , 2008, PloS one.

[33]  David K Menon,et al.  Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans , 2008, The Journal of Neuroscience.

[34]  Martin P Paulus,et al.  Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain. , 2008, Archives of general psychiatry.

[35]  L. Becerra,et al.  Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain , 2008, PloS one.

[36]  M. Ferrari,et al.  Frontal lobe structure and executive function in migraine patients , 2008, Neuroscience Letters.

[37]  M. Ferrari,et al.  Attack Frequency and Disease Duration as Indicators for Brain Damage in Migraine , 2008, Headache.

[38]  J. Rasker,et al.  500 HIPPOCAMPUS DYSFUNCTION MAY EXPLAIN SYMPTOMS OF FIBROMYALGIA SYNDROME , 2008, The Journal of rheumatology.

[39]  Kun-Woo Park,et al.  Regional Grey Matter Changes in Patients With Migraine: A Voxel-Based Morphometry Study , 2008, Cephalalgia : an international journal of headache.

[40]  Irene Tracey,et al.  Investigation into the neural correlates of emotional augmentation of clinical pain , 2008, NeuroImage.

[41]  Daniel J Clauw,et al.  Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. , 2008, Arthritis and rheumatism.

[42]  Richard G. Wise,et al.  Physiological noise modelling for spinal functional magnetic resonance imaging studies , 2008, NeuroImage.

[43]  J. Bueller,et al.  Reduced Brainstem Inhibition during Anticipated Pelvic Visceral Pain Correlates with Enhanced Brain Response to the Visceral Stimulus in Women with Irritable Bowel Syndrome , 2008, The Journal of Neuroscience.

[44]  C. L. Kwan,et al.  CORTICAL THINNING IN IBS: IMPLICATIONS FOR HOMEOSTATIC, ATTENTION, AND PAIN PROCESSING , 2008, Neurology.

[45]  U. Bogdahn,et al.  Subtle Grey Matter Changes Between Migraine Patients and Healthy Controls , 2008, Cephalalgia : an international journal of headache.

[46]  L. Pinessi,et al.  Voxel‐Based Morphometry Reveals Gray Matter Abnormalities in Migraine , 2007, Headache.

[47]  R. Luerding,et al.  Striatal grey matter increase in patients suffering from fibromyalgia – A voxel-based morphometry study , 2007, PAIN.

[48]  J. Zubieta,et al.  Placebo effects on human μ-opioid activity during pain , 2007, Proceedings of the National Academy of Sciences.

[49]  David A Seminowicz,et al.  Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain? , 2007, The Journal of Neuroscience.

[50]  Katja Wiech,et al.  Anticipatory brainstem activity predicts neural processing of pain in humans , 2007, Pain.

[51]  Khek Yu Ho,et al.  Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls , 2006, Pain.

[52]  D. Chialvo,et al.  Chronic Pain and the Emotional Brain: Specific Brain Activity Associated with Spontaneous Fluctuations of Intensity of Chronic Back Pain , 2006, The Journal of Neuroscience.

[53]  Bogdan Draganski,et al.  Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients , 2006, Pain.

[54]  R. Baron,et al.  painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain , 2006, Current medical research and opinion.

[55]  Irene Tracey,et al.  An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients , 2006, NeuroImage.

[56]  Irene Tracey,et al.  Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: A diffusion tensor imaging study in healthy controls , 2006, Pain.

[57]  Massimo Filippi,et al.  Brain Gray Matter Changes in Migraine Patients With T2-Visible Lesions: A 3-T MRI Study , 2006, Stroke.

[58]  J. Zubieta,et al.  Neurobiological Mechanisms of the Placebo Effect , 2005, The Journal of Neuroscience.

[59]  A Straube,et al.  Gray matter decrease in patients with chronic tension type headache , 2005, Neurology.

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

[61]  Raymond J. Dolan,et al.  Modulation of pain processing in hyperalgesia by cognitive demand , 2005, NeuroImage.

[62]  Emeran A. Mayer,et al.  Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis , 2005, Pain.

[63]  M. Bushnell,et al.  Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome , 2005, Pain.

[64]  Pierre Arsenault,et al.  Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition , 2005, Pain.

[65]  Giovanni Giulietti,et al.  Issues about the fMRI of the human spinal cord. , 2004, Magnetic resonance imaging.

[66]  A. Apkarian,et al.  Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density , 2004, The Journal of Neuroscience.

[67]  A. Nirkko,et al.  Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls , 2004, Gut.

[68]  H. Fields.  State-dependent opioid control of pain , 2004, Nature Reviews Neuroscience.

[69]  Till Sprenger,et al.  Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain—an fMRI analysis , 2004, Pain.

[70]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[71]  S. Kapur,et al.  Direct Activation of the Ventral Striatum in Anticipation of Aversive Stimuli , 2003, Neuron.

[72]  J. Detre,et al.  Arterial spin labeling perfusion fMRI with very low task frequency , 2003, Magnetic resonance in medicine.

[73]  E. Bullmore,et al.  The effect of negative emotional context on neural and behavioural responses to oesophageal stimulation. , 2003, Brain : a journal of neurology.

[74]  Patrick W Stroman,et al.  Functional imaging of the rat cervical spinal cord , 2002, Journal of magnetic resonance imaging : JMRI.

[75]  D. Bars.  The whole body receptive field of dorsal horn multireceptive neurones , 2002, Brain Research Reviews.

[76]  Serge Marchand,et al.  Odors modulate pain perception A gender-specific effect , 2002, Physiology & Behavior.

[77]  Igor D. Grachev,et al.  Decreased Levels of N-Acetylaspartate in Dorsolateral Prefrontal Cortex in a Case of Intractable Severe Sympathetically Mediated Chronic Pain (Complex Regional Pain Syndrome, Type I) , 2002, Brain and Cognition.

[78]  G. Gebhart,et al.  Chronic pain and medullary descending facilitation , 2002, Trends in Neurosciences.

[79]  Daniel J Clauw,et al.  Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. , 2002, Arthritis and rheumatism.

[80]  Carolyn C. Meltzer,et al.  Cerebral Responses to Noxious Thermal Stimulation in Chronic Low Back Pain Patients and Normal Controls , 2002, NeuroImage.

[81]  G. Pagnoni,et al.  Does Anticipation of Pain Affect Cortical Nociceptive Systems? , 2002, The Journal of Neuroscience.

[82]  Ravi S. Menon,et al.  Imaging Attentional Modulation of Pain in the Periaqueductal Gray in Humans , 2002, The Journal of Neuroscience.

[83]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[84]  S. Clare,et al.  Imaging how attention modulates pain in humans using functional MRI. , 2002, Brain : a journal of neurology.

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

[86]  M. Catherine Bushnell,et al.  Cognitive modulation of pain: how do attention and emotion influence pain processing? , 2002, Pain.

[87]  P. Matthews,et al.  Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network , 2001, The Journal of Neuroscience.

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

[89]  J Mazziotta,et al.  A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[90]  F. McGlone,et al.  Counter-stimulatory effects on pain perception and processing are significantly altered by attention: an fMRI study. , 2001 .

[91]  A. V. Apkarian,et al.  Brain chemistry reflects dual states of pain and anxiety in chronic low back pain , 2001, NeuroImage.

[92]  S. Derbyshire,et al.  Cerebral Activation in Patients With Irritable Bowel Syndrome and Control Subjects During Rectosigmoid Stimulation , 2001, Psychosomatic medicine.

[93]  M. Verbaten,et al.  Affective pictures processing, attention, and pain tolerance , 2001, Pain.

[94]  Randolph C. Arnau,et al.  Pain and Emotion: Effects of Affective Picture Modulation , 2001, Psychosomatic medicine.

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

[96]  B. McEwen,et al.  Effects of adverse experiences for brain structure and function , 2000, Biological Psychiatry.

[97]  M. Honda,et al.  Expectation of Pain Enhances Responses to Nonpainful Somatosensory Stimulation in the Anterior Cingulate Cortex and Parietal Operculum/Posterior Insula: an Event-Related Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[98]  D. Price.  Psychological and neural mechanisms of the affective dimension of pain. , 2000, Science.

[99]  S. Stone-Elander,et al.  Pain-related cerebral activation is altered by a distracting cognitive task , 2000, Pain.

[100]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[101]  Ravi S. Menon,et al.  Dissociating pain from its anticipation in the human brain. , 1999, Science.

[102]  S. Stone-Elander,et al.  Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study , 1999, Neuroscience Letters.

[103]  K L Casey,et al.  Variability of laser-evoked potentials: attention, arousal and lateralized differences. , 1993, Electroencephalography and clinical neurophysiology.

[104]  Nikolaus M. Szeverenyi,et al.  Persistent pain inhibits contralateral somatosensory cortical activity in humans , 1992, Neuroscience Letters.

[105]  J. Coyle,et al.  Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies , 1991, Neuroscience.

[106]  C. Cleeland,et al.  The effects of induced mood on laboratory pain , 1991, Pain.

[107]  Karl J. Friston,et al.  Cortical and subcortical localization of response to pain in man using positron emission tomography , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[108]  Alan C. Evans,et al.  Multiple representations of pain in human cerebral cortex. , 1991, Science.

[109]  M. Palkovits,et al.  Effect of optic nerve transection onN-acetylaspartylglutamate immunoreactivity in the primary and accessory optic projection systems in the rat , 1991, Brain Research.

[110]  H. Fields,et al.  Anatomy and physiology of a nociceptive modulatory system. , 1985, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[111]  M. Glabus,et al.  Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features. , 2009, The journal of pain : official journal of the American Pain Society.

[112]  B. Pfleiderer,et al.  Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI Study , 2009, Journal of Neural Transmission.

[113]  A. Apkarian,et al.  Representation of pain in the brain , 2006 .

[114]  Harjot Sidhu,et al.  Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients. , 2006, Gastroenterology.

[115]  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.

[116]  D. Louis Collins,et al.  Automatic 3‐D model‐based neuroanatomical segmentation , 1995 .

[117]  L. Villanueva,et al.  The activation of bulbo-spinal controls by peripheral nociceptive inputs: diffuse noxious inhibitory controls. , 1995, Biological research.

[118]  P. Wall,et al.  Textbook of pain , 1989 .

[119]  W. Penfield.  The Cerebral Cortex of Man , 1950 .