Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans.

Intense itch and urge to scratch are the major symptoms of many chronic skin ailments, which are increasingly common. Vicious itch-scratch cycles are readily established and may diminish quality of life for those afflicted. We investigated peripheral and central processing of two types of itch sensation elicited by skin-prick tests of histamine and allergen solutions. Itch-related skin blood flow changes were measured by laser Doppler in 14 subjects responsive to type I allergens and 14 nonatopic subjects. In addition, this study examined central processing of both types of itch using functional magnetic resonance imaging (fMRI). Itch perception and blood flow changes were significantly greater when itch was induced by allergens compared with histamine. Both types of itch correlated significantly with activity in the genual anterior cingulate, striatum, and thalamus. Moreover, itch elicited by allergens activated orbitofrontal, supplementary motor, and posterior parietal areas. Histamine-induced itch also significantly correlated with activation in the insula bilaterally. The identification of limbic and ventral prefrontal activation in two types of itch processing likely reflects the subjects' desire to relieve the itch sensation by scratching, and these regions have been repeatedly associated with motivation processing. A dysfunction of the striato-thalamo-orbitofrontal circuit is believed to underlie the failure to regulate motivational drive in disorders associated with strong urges, e.g., addiction and obsessive compulsive disorder. The patterns of itch-induced activation reported here may help explain why chronic itch sufferers frequently self-harm through uncontrollable itch-scratch cycles.

[1]  K. Berman,et al.  Cerebral Cortex doi:10.1093/cercor/bhj004 Neural Coding of Distinct Statistical Properties of Reward Information in Humans , 2005 .

[2]  K. Fast,et al.  Noxious heat and scratching decrease histamine-induced itch and skin blood flow. , 2005, The Journal of investigative dermatology.

[3]  M. Kringelbach.  The human orbitofrontal cortex: linking reward to hedonic experience , 2005, Nature Reviews Neuroscience.

[4]  R. Stark,et al.  Brain activation by histamine prick test-induced itch. , 2005, The Journal of investigative dermatology.

[5]  B. Vogt.  Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[6]  T. Lotti,et al.  Itch, pain, and metaesthetic sensation , 2005, Dermatologic therapy.

[7]  Rajesh Balkrishnan,et al.  The Burden of Atopic Dermatitis: Impact on the Patient, Family, and Society , 2005, Pediatric dermatology.

[8]  R. Wise,et al.  How can drug addiction help us understand obesity? , 2005, Nature Neuroscience.

[9]  T. Yoshiura,et al.  Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: A functional magnetic resonance imaging study , 2005, Biological Psychiatry.

[10]  Yu-Shin Ding,et al.  Behavioral / Systems / Cognitive Activation of Orbital and Medial Prefrontal Cortex by Methylphenidate in Cocaine-Addicted Subjects But Not in Controls : Relevance to Addiction , 2005 .

[11]  M. Schmelz,et al.  Electrically evoked itch in humans , 2005, Pain.

[12]  M. Yücel,et al.  Addiction, a condition of compulsive behaviour? Neuroimaging and neuropsychological evidence of inhibitory dysregulation. , 2004, Addiction.

[13]  J. Daniel Ragland,et al.  Images of desire: food-craving activation during fMRI , 2004, NeuroImage.

[14]  Jonathan D. Cohen,et al.  Conflict monitoring and anterior cingulate cortex: an update , 2004, Trends in Cognitive Sciences.

[15]  S. Whiteside,et al.  A meta–analysis of functional neuroimaging in obsessive–compulsive disorder , 2004, Psychiatry Research: Neuroimaging.

[16]  Samuel M. McClure,et al.  Separate Neural Systems Value Immediate and Delayed Monetary Rewards , 2004, Science.

[17]  M. Greaves,et al.  Itch: More than Skin Deep , 2004, International Archives of Allergy and Immunology.

[18]  Mathias Schreckenberger,et al.  Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. , 2004, The American journal of psychiatry.

[19]  M. Walton,et al.  Action sets and decisions in the medial frontal cortex , 2004, Trends in Cognitive Sciences.

[20]  M. Delgado,et al.  Motivation-dependent responses in the human caudate nucleus. , 2004, Cerebral cortex.

[21]  M. Phillips,et al.  Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. , 2004, Archives of general psychiatry.

[22]  M. Behrmann,et al.  Parietal cortex and attention , 2004, Current Opinion in Neurobiology.

[23]  Mark W. Woolrich,et al.  Multilevel linear modelling for FMRI group analysis using Bayesian inference , 2004, NeuroImage.

[24]  B. Aouizerate,et al.  Pathophysiology of obsessive–compulsive disorder A necessary link between phenomenology, neuropsychology, imagery and physiology , 2004, Progress in Neurobiology.

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

[26]  J. Parkinson,et al.  Dissociable Contributions of the Human Amygdala and Orbitofrontal Cortex to Incentive Motivation and Goal Selection , 2003, The Journal of Neuroscience.

[27]  Stephen M. Smith,et al.  General multilevel linear modeling for group analysis in FMRI , 2003, NeuroImage.

[28]  Kazuhiko Yanai,et al.  Imaging of central itch modulation in the human brain using positron emission tomography , 2003, Pain.

[29]  Kazunori Sato,et al.  The Human Prefrontal and Parietal Association Cortices Are Involved in NO-GO Performances: An Event-Related fMRI Study , 2002, NeuroImage.

[30]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[31]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

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

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

[34]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[35]  Frank Munz,et al.  Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies , 2001, Pain.

[36]  M. Schmelz.  A neural pathway for itch , 2001, Nature Neuroscience.

[37]  A. Craig,et al.  Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch , 2001, Nature Neuroscience.

[38]  M Schwaiger,et al.  Processing of histamine-induced itch in the human cerebral cortex: a correlation analysis with dermal reactions. , 2000, The Journal of investigative dermatology.

[39]  E. Carstens,et al.  Superficial dorsal horn neurons identified by intracutaneous histamine: chemonociceptive responses and modulation by morphine. , 2000, Journal of neurophysiology.

[40]  David Borsook,et al.  Noxious hot and cold stimulation produce common patterns of brain activation in humans: a functional magnetic resonance imaging study , 2000, Neuroscience Letters.

[41]  J S Fowler,et al.  Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. , 2000, Cerebral cortex.

[42]  R. Elliott,et al.  Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies. , 2000, Cerebral cortex.

[43]  Laidlaw,et al.  Pruritus: more scratch than itch , 1999, Clinical and experimental dermatology.

[44]  C. Wahlgren.  Itch and Atopic Dermatitis: An Overview , 1999, The Journal of dermatology.

[45]  U. Gieler,et al.  Observations during Itch-Inducing Lecture , 1999, Dermatology and Psychosomatics / Dermatologie und Psychosomatik.

[46]  G. Crombez,et al.  Pain demands attention: a cognitive-affective model of the interruptive function of pain. , 1999, Psychological bulletin.

[47]  Hermann O. Handwerker,et al.  Specific C-Receptors for Itch in Human Skin , 1997, The Journal of Neuroscience.

[48]  R. Turner,et al.  Characterizing Dynamic Brain Responses with fMRI: A Multivariate Approach , 1995, NeuroImage.

[49]  M Ingvar,et al.  Urge to scratch represented in the human cerebral cortex during itch. , 1994, Journal of neurophysiology.

[50]  Alan C. Evans,et al.  Distributed processing of pain and vibration by the human brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  J. Price,et al.  The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys , 1993, The Journal of comparative neurology.

[52]  Alan C. Evans,et al.  A Three-Dimensional Statistical Analysis for CBF Activation Studies in Human Brain , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[53]  Smith Tf.  Allergy testing in clinical practice. , 1992 .

[54]  T. F. Smith.  Allergy testing in clinical practice. , 1992, Annals of allergy.

[55]  U. Pipkorn,et al.  Wheal-and-flare reactions induced by allergen and histamine: evaluation of blood flow with laser Doppler flowmetry. , 1988, The Journal of allergy and clinical immunology.

[56]  R. P. Warin,et al.  Textbook of Dermatology , 1987, Bristol Medico-Chirurgical Journal.

[57]  Arthur Rook,et al.  TEXTBOOK OF DERMATOLOGY , 2007 .