Abstract
Chronic itch is multidimensional phenomenon associated with emotional and cognitive aspects of suffering that causes the urge to scratch. The brain is the final terminal to receive itch-related neural signals from the body and to process them. Thus, it is important to better understand the mechanism of itch and its behavioral response of scratching in the brain. Brain imaging studies using positron emission tomography, functional MRI, electroencephalography, and magnetoencephalography have been conducted to understand the cerebral mechanism of itch mainly in healthy subjects using experimental itch models. Several brain imaging studies have investigated this mechanism in chronic itch patients to better understand the pathophysiology of chronic itch in the central nervous system. Pharmacological functional MRI studies add to our understanding of drug-effects on brain systems. Recently, this technique was used to investigate how a kappa opioid drug butoprhanol, modulates the processing of itch in the brain. Other promising treatments targeting the brain such as non-invasive transcranial Direct Current Stimulation that has been used for treatments of chronic pain has been reported for itch relief. In this chapter, we review the current progress in neuroimaging research of itch and scratch and its treatments.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Akiyama T, Carstens E. Neural processing of itch. Neuroscience. 2013;250:697–714.
Antal A, Brepohl N, Poreisz C, Boros K, Csifcsak G, Paulus W. Transcranial direct current stimulation over somatosensory cortex decreases experimentally induced acute pain perception. Clin J Pain. 2008;24:56–63.
Antal A, Terney D, Kühnl S, Paulus W. Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage. 2010;39:890–903.
Bär KJ, Gaser C, Nenadic I, Sauer H. Transient activation of a somatosensory area in painful hallucinations shown by fMRI. Neuroreport. 2002;13:805–8.
Bornhövd K, Quante M, Glauche V, Bromm B, Weiller C, Büchel C. Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. Brain. 2002;125:1326–36.
Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006;129:564–83.
DaSilva AF, Mendonca ME, Zaghi S, Lopes M, Dossantos MF, Spierings EL, Bajwa Z, Datta A, Bikson M, Fregni F. tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine. Headache. 2012;52:1283–95.
Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006;54:527–31.
de Andrade DC, Mhalla A, Adam F, Texeira MJ, Bouhassira D. Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids. Pain. 2011;152:320–6.
Deecke L, Kornhuber HH. An electrical sign of participation of the mesial ‘supplementary’ motor cortex in human voluntary finger movement. Brain Res. 1978;159:473–6.
Dong WK, Salonen LD, Kawakami Y, Shiwaku T, Kaukoranta EM, Martin RF. Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys. Brain Res. 1989;484:314–24.
Dong WK, Chudler EH, Sugiyama K, Roberts VJ, Hayashi T. Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys. J Neurophysiol. 1994;72:542–64.
Drzezga A, Darsow U, Treede RD, Siebner H, Frisch M, Munz F, Weilke F, Ring J, Schwaiger M, Bartenstein P. Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies. Pain. 2001;92:295–305.
Emerson NM, Zeidan F, Lobanov OV, Hadsel MS, Martucci KT, Quevedo AS, Starr CJ, Nahman-Averbuch H, Weissman-Fogel I, Granovsky Y, Yarnitsky D, Coghill RC. Pain sensitivity is inversely related to regional grey matter density in the brain. Pain. 2014;155:566–73.
Faymonville ME, Boly M, Laureys S. Functional neuroanatomy of the hypnotic state. J Physiol Paris. 2006;99:463–9.
Filbey FM, Claus E, Audette AR, Niculescu M, Banich MT, Tanabe J, Du YP, Hutchison KE. Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry. Neuropsychopharmacology. 2008;33:1391–401.
Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122:197–209.
Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum. 2006;54:3988–98.
Fregni F, Freedman S, Pascual-Leone A. Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurol. 2007;6:188–91.
Fried I, Katz A, McCarthy G, Sass KJ, Williamson P, Spencer SS, Spencer DD. Functional organization of human supplementary motor cortex studied by electrical stimulation. J Neurosci. 1991;11:3656–66.
Frot M, Magnin M, Mauguière F, Garcia-Larrea L. Human SII and posterior insula differently encode thermal laser stimuli. Cereb Cortex. 2007;17:610–20.
Gemba H, Hashimoto S, Sasaki K. Cortical field potentials preceding visually initiated hand movements in the monkey. Exp Brain Res. 1981;42:435–41.
Gemba H, Sasaki K, Tsujimoto T. Cortical field potentials associated with hand movements triggered by warning and imperative stimuli in the monkey. Neurosci Lett. 1990;113:275–80.
Herde L, Forster C, Strupf M, Handwerker HO. Itch induced by a novel method leads to limbic deactivations a functional MRI study. J Neurophysiol. 2007;98:2347–56.
Heide W, Binkofski F, Seitz RJ, Posse S, Nitschke MF, Freund HJ, Kömpf D. Activation of frontoparietal cortices during memorized triple-step sequences of saccadic eye movements: an fMRI study. Eur J Neurosci. 2001;13:1177–89.
Hsieh JC, Hägermark O, Ståhle-Bäckdahl M, Ericson K, Eriksson L, Stone-Elander S, Ingvar M. Urge to scratch represented in the human cerebral cortex during itch. J Neurophysiol. 1994;72:3004–8.
Holle H, Warne K, Seth AK, Critchley HD, Ward J. Neural basis of contagious itch and why some people are more prone to it. Proc Natl Acad Sci U S A. 2012;109:19816–21.
Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol. 2009;161:1072–80.
Izuma K, Saito DN, Sadato N. Processing of social and monetary rewards in the human striatum. Neuron. 2008;58:284–94.
Knotkova H, Portenoy RK, Cruciani RA. Transcranial direct current stimulation (tDCS) relieved itching in a patient with chronic neuropathic pain. Clin J Pain. 2013;29:621–2.
Kühn S, Gallinat J. The neural correlates of subjective pleasantness. Neuroimage. 2012;64:289–94.
LaBar KS, Gitelman DR, Parrish TB, Mesulam M. Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects. Neuroimage. 1999;10:695–704.
Lacourse MG, Orr EL, Cramer SC, Cohen MJ. Brain activation during execution and motor imagery of novel and skilled sequential hand movements. Neuroimage. 2005;27:505–19.
Leknes SG, Bantick S, Willis CM, Wilkinson JD, Wise RG, Tracey I. Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans. J Neurophysiol. 2007;97:415–22.
Lima MC, Fregni F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology. 2008;70:2329–37.
Mantovani A, Rossi S, Bassi BD, Simpson HB, Fallon BA, Lisanby SH. Modulation of motor cortex excitability in obsessive-compulsive disorder: an exploratory study on the relations of neurophysiology measures with clinical outcome. Psychiatry Res. 2013;210:1026–32.
McCabe C, Rolls ET. Umami: a deliciousflavor formed by convergence of taste and olfactory pathways in the human brain. Eur J Neurosci. 2007;25:1855–64.
Mochizuki H, Tashiro M, Kano M, Sakurada Y, Itoh M, Yanai K. Investigation of the central itch modulation system using positron emission tomography. Pain. 2003;105:339–46.
Mochizuki H, Sadato N, Saitoh D, Toyoda H, Tashiro M, Okamura N, Yanai K. Neural correlates of perceptual difference between itching and pain using functional magnetic resonance imaging. Neuroimage. 2007;36:706–17. Erratum in Neuroimage. 2008; 39: 911–912.
Mochizuki H, Inui K, Yamashiro K, Ootsuru N, Kakigi R. Itching-related somatosensory evoked potentials. Pain. 2008;138:598–603.
Mochizuki H, Inui K, Tanabe HC, Akiyama LF, Otsuru N, Yamashiro K, Sasaki A, Nakata H, Sadato N, Kakigi R. Time course of activity in itch-related brain regions: a combined MEG-fMRI study. J Neurophysiol. 2009;102:2657–66.
Mochizuki H, Baumgärtner U, Kamping S, Ruttorf M, Schad LR, Flor H, Kakigi R, Treede RD. Cortico-subcortical activation patterns for itch and pain imagery. Pain. 2013;154:1989–98.
Mochizuki H, Tanaka S, Morita T, Wasaka T, Sadato N, Kakigi R. The cerebral representation of scratching-induced pleasantness. J Neurophysiol. 2014;111:488–98.
Mochizuki H, Papoiu AD, Nattkemper LA, Lin AC, Kraft RA, Coghill RC, Yosipovitch G. Scratching induces overactivity in motor-related regions and reward system in chronic itch patients. J Invest Dermatol. 2015;135(11):2814–23. doi: 10.1038/jid.2015.223.
Mori F, Codecà C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, Bernardi G, Koch G, Centonze D. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010;11:436–42.
Nakagawa K, Mochizuki H, Koyama S, Tanaka S, Sadato N, Kakigi R. A transcranial direct current stimulation over the sensorimotor cortex modulates the itch sensation induced by histamine. Clin Neurophysiol. 2016;127(1):827–32. doi: 10.1016/j.clinph.2015.07.003.
Niemeier V, Kupferb J, Gielerc U. Observations during an itch-inducing lecture. Dermatol Psychosom. 2000;1:15–8.
Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 2008;1:206–23.
Ogiso T, Kobayashi K, Sugishita M. The precuneus in motor imagery: a magnetoencephalographic study. Neuroreport. 2000;11:1345–9.
Papoiu AD, Wang H, Coghill RC, Chan YH, Yosipovitch G. Contagious itch in humans: a study of visual ‘transmission’ of itch in atopic dermatitis and healthy subjects. Br J Dermatol. 2011;164:1299–303.
Papoiu AD, Coghill RC, Kraft RA, Wang H, Yosipovitch G. A tale of two itches common features and notable differences in brain activation evoked by cowhage and histamine induced itch. Neuroimage. 2012;59:3611–23.
Papoiu AD, Nattkemper LA, Sanders KM, Kraft RA, Chan YH, Coghill RC, Yosipovitch G. Brain’s reward circuits mediate itch relief. a functional MRI study of active scratching. PLoS One. 2013;8, e82389.
Papoiu AD, Emerson NM, Patel TS, Kraft RA, Valdes-Rodriguez R, Nattkemper LA, Coghill RC, Yosipovitch G. Voxel-based morphometry and arterial spin labeling fMRI reveal neuropathic and neuroplastic features of brain processing of itch in end-stage-renal-disease. Neurophysiology. 2014;112:1729–38.
Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G. Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study. J Invest Dermatol. 2015;135:560–8.
Peckys D, Landwehrmeyer GB. Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: a 33P in situ hybridization study. Neuroscience. 1999;88:1093–135.
Peckys D, Hurd YL. Prodynorphin and kappa opioid receptor mRNA expression in the cingulate and prefrontal cortices of subjects diagnosed with schizophrenia or affective disorders. Brain Res Bull. 2001;55:619–24.
Roesch MR, Olson CR. Impact of expected reward on neuronal activity in prefrontal cortex, frontal and supplementary eye fields and premotor cortex. J Neurophysiol. 2003;90:1766–89.
Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat Neurosci. 2011;257:257–62.
Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork HE, Handwerker HO. Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol. 2003;89:2441–8.
Schneider G, Ständer S, Burgmer M, Driesch G, Heuft G, Weckesser M. Significant differences in central imaging of histamine-induced itch between atopic dermatitis and healthy subjects. Eur J Pain. 2008;12:834–41.
Schulz-Stu¨bner S, Krings T, Meister IG, Rex S, Thron A, Rossaint R. Clinical hypnosis modulates functional magnetic resonance imaging signal intensities and pain perception in a thermal stimulation paradigm. Reg Anesth Pain Med. 2004;29:549–56.
Simon SR, Meunier M, Piettre L, Berardi AM, Segebarth CM, Boussaoud D. Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI. J Neurophysiol. 2002;88:2047–57.
Szameitat AJ, Shen S, Sterr A. Motor imagery of complex everyday movements. An fMRI study. Neuroimage. 2007;34:702–13.
Tamura Y, Hoshiyama M, Inui K, Nakata H, Qiu Y, Ugawa Y, Inoue K, Kakigi R. Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation. Neurology. 2004;62:2176–81.
Tamura Y, Okabe S, Ohnishi TN, Saito D, Arai N, Mochio S, Inoue K, Ugawa Y. Effects of 1-Hz repetitive transcranial magnetic stimulation on acute pain induced by capsaicin. Pain. 2004;107:107–15.
Timmermann L, Ploner M, Haucke K, Schmitz F, Baltissen R, Schnitzler A. Differential coding of pain intensity in the human primary and secondary somatosensory cortex. J Neurophysiol. 2001;86:1499–503.
Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag. 2009;2:353–61.
Walter B, Sadlo MN, Kupfer J, Niemeier V, Brosig B, Stark R, Vaitl D, Gieler U. Brain activation by histamine prick test-induced itch. J Invest Dermatol. 2005;125:380–2.
Yosipovitch G, Goon AT, Wee J, Chan YH, Zucker I, Goh CL. Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus. Int J Dermatol. 2002;41:212–6.
Yosipovitch G, Ishiuji Y, Patel TS, Hicks MI, Oshiro Y, Kraft RA, Winnicki E, Coghill RC. The brain processing of scratching. J Invest Dermatol. 2008;128:1806–11.
Acknowledgement
The authors wish to thank Mrs. Alina Shevchenko and Dr. Alexandre D Papoiu for their assistance.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer-Verlag London
About this chapter
Cite this chapter
Mochizuki, H., Yosipovitch, G. (2016). Central Representation of Itch. In: Misery, L., Ständer, S. (eds) Pruritus. Springer, Cham. https://doi.org/10.1007/978-3-319-33142-3_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-33142-3_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33140-9
Online ISBN: 978-3-319-33142-3
eBook Packages: MedicineMedicine (R0)