Daily physical complaints and hippocampal function: An fMRI study of pain modulation by anxiety

Pain is a popular physical complaint in human. It is known that experimental anxiety modulates pain processing through hippocampal amplification, whereas it is not known whether a similar experimental reaction is related to daily physical complaints known as 'somatization'. The purpose of this study is to investigate the neural correlates of pain modulation induced by anxiety, particularly in the hippocampus, and how individual differences in this neural reaction relate to somatization. We measured neural response to noxious electrical stimulations, as well as the response to the preceding visual anticipatory cues (which induced low anxiety or high anxiety), by functional magnetic resonance imaging (fMRI). Individual daily physical symptoms were assessed by using the somatization subscale of the Symptom Checklist 90 revised (SCL-90-R). Correlation coefficients between the neural activations and the somatization scores were calculated. We found that manifestation of daily physical symptoms was related to smaller differences in hippocampus activation between high and low anxiety states, suggesting that the ability of the hippocampus to distinguish anxiety states was weakened by the chronic condition that caused the daily physical symptoms. The proper inhibition of neural activation in low anxiety states in the hippocampus and the anterior insula was observed to occur in companionship with lower daily physical complaints. These findings indicate that anxiety's alteration of the network that includes the hippocampus and that is associated with pain modulation underlies the manifestation of somatization.

[1]  S. Minoshima,et al.  Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. , 2003, Brain : a journal of neurology.

[2]  B. Rosen,et al.  A Functional Magnetic Resonance Imaging Study on the Neural Mechanisms of Hyperalgesic Nocebo Effect , 2008, The Journal of Neuroscience.

[3]  Anthony K. P. Jones,et al.  Pain processing during three levels of noxious stimulation produces differential patterns of central activity , 1997, Pain.

[4]  Koraly Pérez-Edgar,et al.  The role of temperament in somatic complaints among young female adults , 2012, Journal of health psychology.

[5]  H. Critchley The human cortex responds to an interoceptive challenge. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Critchley,et al.  Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response , 2010, Brain Structure and Function.

[7]  Richard J. Davidson,et al.  Individual Differences in the Effects of Perceived Controllability on Pain Perception: Critical Role of the Prefrontal Cortex , 2007, Journal of Cognitive Neuroscience.

[8]  Anthony K. P. Jones,et al.  The cortical representation of pain , 1999, PAIN.

[9]  T. Hendler,et al.  Individual sensitivity to pain expectancy is related to differential activation of the hippocampus and amygdala , 2009, Human brain mapping.

[10]  A. Apkarian,et al.  Parsing pain perception between nociceptive representation and magnitude estimation. , 2009, Journal of neurophysiology.

[11]  L. Mayes,et al.  Preoperative anxiety and postoperative pain in women undergoing hysterectomy. A repeated-measures design. , 2000, Journal of psychosomatic research.

[12]  J. O'Doherty,et al.  Empathy for Pain Involves the Affective but not Sensory Components of Pain , 2004, Science.

[13]  Roland Peyron,et al.  Spatial segregation of somato-sensory and pain activations in the human operculo-insular cortex , 2012, NeuroImage.

[14]  T. Mima,et al.  Functional localization of pain perception in the human brain studied by PET , 1997, Neuroreport.

[15]  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.

[16]  A. Barsky,et al.  Functional Somatic Syndromes , 1999, Annals of Internal Medicine.

[17]  H. Breiter,et al.  Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study , 1999, Magnetic resonance in medicine.

[18]  Thomas Weiss,et al.  Do words hurt? Brain activation during the processing of pain-related words , 2010, PAIN.

[19]  Joseph E LeDoux,et al.  Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study , 1998, Neuron.

[20]  Jean Decety,et al.  Empathy and judging other's pain: an fMRI study of alexithymia. , 2007, Cerebral cortex.

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

[22]  Does somatosensory amplification decrease with antidepressant treatment? , 2005, Psychosomatics.

[23]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[24]  C. Kubo,et al.  The reliability and validity of a Japanese version of symptom checklist 90 revised , 2008, BioPsychoSocial medicine.

[25]  L. Jarrard,et al.  The hippocampus and inhibitory learning: a ‘Gray’ area? , 2004, Neuroscience & Biobehavioral Reviews.

[26]  K. Kroenke Studying Symptoms: Sampling and Measurement Issues , 2001, Annals of Internal Medicine.

[27]  V. Arolt,et al.  Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review , 2009, PloS one.

[28]  J. Vlaeyen,et al.  The effects of failure feedback and pain-related fear on pain report, pain tolerance, and pain avoidance in chronic low back pain patients , 2001, Pain.

[29]  R. Sternbach Chapter 7 – PSYCHOLOGICAL DIMENSIONS AND PERCEPTUAL ANALYSES, INCLUDING PATHOLOGIES OF PAIN , 1978 .

[30]  A. Apkarian,et al.  Pain perception in relation to emotional learning , 2008, Current Opinion in Neurobiology.

[31]  Elliot A. Stein,et al.  Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning , 2007 .

[32]  B. Given,et al.  Treating patients with medically unexplained symptoms in primary care , 2003, Journal of General Internal Medicine.

[33]  Stephan Bender,et al.  Am I safe? The ventrolateral prefrontal cortex ‘detects’ when an unpleasant event does not occur , 2007, NeuroImage.

[34]  Richard J. Brown,et al.  Somatoform dissociation and somatosensory amplification are differentially associated with attention to the tactile modality following exposure to body-related stimuli. , 2007, Journal of psychosomatic research.

[35]  Karl J. Friston,et al.  Amygdala–Hippocampal Involvement in Human Aversive Trace Conditioning Revealed through Event-Related Functional Magnetic Resonance Imaging , 1999, The Journal of Neuroscience.

[36]  Monika Sommer,et al.  Combined measurement of event-related potentials (ERPs) and fMRI. , 2003, Acta neurobiologiae experimentalis.

[37]  Nikolaus Weiskopf,et al.  Anterolateral Prefrontal Cortex Mediates the Analgesic Effect of Expected and Perceived Control over Pain , 2006, The Journal of Neuroscience.

[38]  Greg D. Gale,et al.  Hippocampus and contextual fear conditioning: Recent controversies and advances , 2001, Hippocampus.

[39]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

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

[41]  P. Corr,et al.  A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance , 2004, Neuroscience & Biobehavioral Reviews.

[42]  J. Gray,et al.  The neuropsychology of anxiety: reprise. , 1996, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[43]  D. Ciccone,et al.  Non-organic symptom reporting in patients with chronic non-malignant pain , 1996, Pain.

[44]  A. Jula,et al.  Alexithymia and Somatization in General Population , 2008, Psychosomatic medicine.

[45]  Elena Peltz,et al.  Functional connectivity of the human insular cortex during noxious and innocuous thermal stimulation , 2011, NeuroImage.

[46]  C. Sorg,et al.  Altered cerebral response to noxious heat stimulation in patients with somatoform pain disorder , 2008, PAIN®.

[47]  Fausta Lui,et al.  Does It Look Painful or Disgusting? Ask Your Parietal and Cingulate Cortex , 2008, The Journal of Neuroscience.

[48]  S. Chaturvedi,et al.  Somatization, somatosensory amplification, attribution styles and illness behaviour: A review , 2006, International review of psychiatry.

[49]  D. Bates,et al.  Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. , 2005, Archives of general psychiatry.

[50]  M. Norris,et al.  Active and passive coping strategies in chronic pain patients , 1996, Pain.

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

[52]  K. Wells,et al.  Somatization in the community: relationship to disability and use of services. , 1987, American journal of public health.

[53]  G. Duncan,et al.  Is there a role for the parietal lobes in the perception of pain? , 2003, Advances in neurology.

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

[55]  A. Barsky,et al.  Hypochondriasis and Somatosensory Amplification , 1990, British Journal of Psychiatry.

[56]  Frank Seifert,et al.  Activation of central sympathetic networks during innocuous and noxious somatosensory stimulation , 2011, NeuroImage.

[57]  Kevin N. Ochsner,et al.  Neural correlates of individual differences in pain-related fear and anxiety , 2006, Pain.