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Urge to scratch represented in the human cerebral cortex during itch
Abstract
1. We used functional positron emission tomography (PET), measuring regional cerebral blood flow (rCBF) as an index of neuronal activity, to investigate the central processing of itch in 10 healthy volunteers subjected to intracutaneous injections of histamine. 2. The study has unraveled a central representation that depicts a motor intention of the urge to scratch contingent on the perception of unpleasant itch. The coactivation of the anterior cingulate cortex (ACC), supplementary motor area (SMA), premotor area (PM), and inferior parietal lobule (IPL) substantiates that the posterior sector of the ACC (Brodmann 24) is related to the sensorial/affectional aspect of the event. The premotor cortical areas (SMA, PM) and the IPL may participate in the preparation of an intended action.
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“Thus, we suggest that the activity in SMA and pre-SMA in the present study reflects an urge to withdraw the hand, rather than anxiety, because this activity was not correlated with the anxiety ratings.”
From Threatening a rubber hand that you feel is yours elicits a cortical anxiety response. (2007) · cites this paper as [29]
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“The earlier brain imaging study has unraveled a coactivation of the anterior cingulate cortex (ACC), motor cortex, and premotor cortex that depicts a motor intention of the urge to scratch (Hsieh et al., 1994).”
BackgroundNocebo-induced modulation of cerebral itch processing – An fMRI study
van de Sand, M. F., Menz, M. M., Sprenger, C., & Büchel, C. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.10.056 · Cited by 38
“Previous studies on itch have reported opercular activation (Hsieh et al., 1994; Papoiu et al., 2012).”
Psychosomatic Aspects of Pruritus
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Transient Receptor Potential Channels and Itch: How Deep Should We Scratch?
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Histamine and Itch Robin L. Thurmond, K. K. (2014) · CRC Press eBooks · doi:10.1201/b16573-14 · Cited by 28
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“Recently, functional neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging (fMRI) have been used to clarify the central mechanism of itching [4,8,15,16].”
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Bassel, C., & Schiff, B. B. (2001) · Neuropsychologia · doi:10.1016/s0028-3932(00)00116-0 · Cited by 26
Central mechanisms of itch: A systematic literature review and meta-analysis
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“Activation in this region was evoked by inducing itch in normal subjects and asking them not to move, implying that motor planning related to the urge to move may be represented in the prefrontal cortex (Hsieh et al., 1994).”
BackgroundIkoma, A. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.09r05fm · Cited by 23
Kim, J. H., Kim, D. H., & Lee, Y. P. (2019) · Techniques in Coloproctology · doi:10.1007/s10151-019-01934-x · Cited by 23
Potentiation of synaptic transmission in Rat anterior cingulate cortex by chronic itch
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“Human imaging studies showed that the ACC is active simultaneously with itch [7, 8].”
Cortical G luK1 kainate receptors modulate scratching in adult mice
Descalzi, G., Chen, T., Koga, K., et al. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12351 · Cited by 22
Some neurophysiological aspects of itch
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“However, this does not rule out the possibility that this area is crucial for other aspects of itch processing, such as stimulus localization [10] or motor planning of the scratch response ([8,9]).”
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Cutaneous sensory nerve fibers are decreased in number after peripheral and central nerve damage
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Le prurit : des avancées physiopathologiques considérables
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Helmchen, C., Palzer, C., Münte, T. F., Anders, S., & Sprenger, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082756 · Cited by 15
“The urge to scratch is reflected in activations of brain regions engaged in the processing of the sensory and affective / motivational aspects of itch and premotor cortical areas involved in the action preparation [29-32].”
BackgroundBOLD responses to itch in the human spinal cord
van de Sand, M. F., Sprenger, C., & Büchel, C. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.12.019 · Cited by 15
“Functional neuroimaging studies employing PET and fMRI revealed a widespread itch-related brain network, comprising the cingulate, parietal, prefrontal, premotor, primary motor, somatosensory and insular cortices (Herde et al., 2007; Hsieh et al., 1994;Mochizuki et al., 2013; Papoiu et al., 2012; Valet et al., 2007).”
Prediction and action in cortical pain processing
Koppel, L., Novembre, G., Kämpe, R., Savallampi, M., & Morrison, I. (2022) · Cerebral Cortex · doi:10.1093/cercor/bhac102 · Cited by 14
“On the perceptual level, intracranial microstimulation of human ACC results in reported feelings of urgency rather than pain sensation (Bancaud et al. 1976; Hsieh et al. 1994).”
BackgroundCentral neural circuits underlying itch sensation
Sun, Y.-G. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00981-8 · Cited by 14
Brain Processing of Itch and Scratching
Mochizuki, H. (2014) · CRC Press eBooks · doi:10.1201/b16573-27 · Cited by 17
Distraction From Itch Shows Brainstem Activation Without Reduction in Experimental Itch Sensation
Stumpf, A., Pfleiderer, B., Schneider, G., Heuft, G., Schmelz, M., Phan, N. Q., Ständer, S., & Burgmer, M. (2017) · Acta Dermato Venereologica · doi:10.2340/00015555-2732 · Cited by 13
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Mochizuki, H., Hernandez, L. E. D. L. C., Yosipovitch, G., Sadato, N., & Kakigi, R. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00555 · Cited by 14
“In itch studies, previous brain imaging studies have identified brain regions activated by itch stimuli including the prefrontal cortex (PFC), supplementary motor area (SMA), premotor cortex (PM), somatosensory cortex, lateral and medial parietal cortex, midcingulate cortex (MCC), claustrum, anrterior insula (aIns), p…”
BackgroundCell Type‐Specific Modulation of Acute Itch Processing in the Anterior Cingulate Cortex
Li, J., Bai, Y., Ge, J., Zhang, Y., Zhao, Q., Li, D., Guo, B., Gao, S., Zhu, Y., Cai, G., et al. (2024) · Advanced Science · doi:10.1002/advs.202403445 · Cited by 12
Brain activation after nasal histamine provocation in house dust mite allergic rhinitis patients
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An atlas of itch-associated neural dynamics in the mouse brain
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“ACC has been associated with various types of urges such as itch (Hsieh et al. 1994), voiding of urine (Kuhtz-Buschbeck et al.”
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Song, S.-G., & Kim, S.-H. (2011) · Journal of the Korean Society of Coloproctology · doi:10.3393/jksc.2011.27.2.54 · Cited by 11
“Methylene blue may be directly toxic to the nerves supplying the perianal skin, thus suppressing the desire to scratch and disrupting the vicious itch-scratch-itch cycle [16].”
Najafi, P., Misery, L., Carré, J., Salem, D. B., & Dufor, O. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.636904 · Cited by 9
“(3) PET Subtraction Intracutaneous injection Histamine 10 Healthy”
BackgroundWhat does brain imaging tell us about itch?
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“First Pain” in Humans: Convergent and Specific Forebrain Responses
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“Early imaging studies revealed painrelated activity in the anterior insula [50-53], but activation during the first 10 s of repetitive noxious heat stimulation shifts from the anterior to the posterior insula as stimulation continues for 45 s [54].”
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“Methylene blue works by severing the nerve endings of the perianal skin’s unmyelinated C-fibers [5], which reduces the urge to scratch [2].”
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“To examine the influence of cognitive control during the experience of itch in future experimental studies will provide precise evidence to inform how the urge to itch may be interrupted via executive function 73 .”
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“69 Contribution of R PMC to the classification performance of our Pre-DM model might be related to its role in regulating avoidance behavior for painful and non-painful stimuli.”
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“Functional neuroimaging investigations in humans have revealed pruritus-correlated hemodynamic changes within the anterior cingulate cortex (ACC) during acute itch processing [11–14].”
Physiology and Pathophysiology of Sneezing and Itching: Mechanisms of the Symptoms
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“…resonance imaging (fMRI) and positron emission tomography (PET) have indicated that the PPC is activated during itch perception, suggesting that the PPC is associated with the processing of itch information (Mochizuki et al., 2003; Leknes et al., 2007; Hsieh et al., 1994; Najafi et al., 2021).”
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“For objective documentation of prurities during itch episodes, positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) have been commonly used in neuroimaging.(5,6) Neuroimaging involves monitoring the brain activities while itching occurs.”
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Chapter 58 Clinical neurophysiology of tics
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“ACC has been associated with various types of urges such as itch (58), voiding of urine (59, 60), coughing (61, 62), and smoking (63).”
Chapter 18 Itch and cold allodynia
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Ural, K., Erdoğan, H., ERDOĞAN, S., et al. (2025) · Bozok Veterinary Sciences · doi:10.58833/bozokvetsci.1704617 · Cited by 1
Placing Placebo in Normal Brain Function with Neuroimaging
Ingvar, M., Petrović, P., & Jensen, K. B. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397928-5.00009-x · Cited by 1
Self-citation
Metadata
- Authors
- Hsieh, J. C., Hagermark, O., Stahle-Backdahl, M., Ericson, K., Eriksson, L., Stone-Elander, S., & Ingvar, M.
- Affiliations
- Karolinska Institutet (SE)
- Department of Clinical Neuroscience, Karolinska Institute/Hospital,Stockholm, Sweden.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1994-12-01
- Volume
- 72
- Issue
- 6
- Pages
- 3004-3008
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W1902361870
- Cited by
- 237
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 10 · 2012: 9
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- pruritus, anterior cingulate cortex, supplementary motor area, premotor cortex, inferior parietal lobule, regional cerebral blood flow, histamine, action preparation, motor intention
- MeSH terms
- Adult, Cerebral Cortex, Cerebrovascular Circulation, Histamine, Humans, Image Processing, Computer-Assisted, Middle Aged, Pruritus, Tomography, Emission-Computed
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