{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T22:03:52Z","timestamp":1774649032245,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T00:00:00Z","timestamp":1374192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fragile-X research foundation of Canada"},{"name":"E. Fidlar Ontario Graduate Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent investigations into the mechanisms mediating itch transmission have focused on spinal mechanisms, whereas few studies have investigated the role of the cerebral cortex in itch\u2010related behaviors. Human imaging studies show that several cortical regions are active in correspondence with itch, including the anterior cingulate cortex (<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>). We present here evidence of cortical modulation of pruritogen\u2010induced scratching behavior. We combine pharmacological, genetic, and electrophysiological approaches to show that cortical GluK1\u2010containing kainate (<jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>) receptors are involved in scratching induced by histamine and non\u2010histamine\u2010dependent itching stimuli. We further show that scratching corresponds with enhanced excitatory transmission in the <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> through <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> receptor modulation of inhibitory circuitry. In addition, we found that inhibiting GluK1\u2010containing <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> receptors in the <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> also reduced behavioral nociceptive responses induced by formalin. Our results reveal a new role of the cortex in pruritogen\u2010induced scratching.<\/jats:p><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12351-fig-0101-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Cortical contribution to pruritogen\u2010induced scratching is shown in an animal model. Through a combination of pharmacological, genetic, and electrophysiological data, we show that cortical GluK1\u2010containing kainate receptors (KAR) are involved in pruritogen\u2010induced scratching. Peripheral application of itching stimuli activates excitatory afferents projecting to ACC layer II\/III pyramidal neurons, initiating presynaptic glutamate (Glu) release which activates postsynaptic AMPA receptors. Simultaneously, presynaptic Glu activates presynaptic KAR located on inhibitory neurons, thereby modulating evoked GABA release and affecting the attenuation of the postsynaptic response.<\/jats:p>","DOI":"10.1111\/jnc.12351","type":"journal-article","created":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T09:07:53Z","timestamp":1371805673000},"page":"636-650","source":"Crossref","is-referenced-by-count":23,"title":["Cortical <scp>G<\/scp>luK1 kainate receptors modulate scratching in adult mice"],"prefix":"10.1111","volume":"126","author":[{"given":"Giannina","family":"Descalzi","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"},{"name":"Center for Neuron and Disease Frontier Institutes of Life Science, and Science and Technology Xi'an Jiaotong University Xian Shanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang\u2010Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"},{"name":"Center for Neuron and Disease Frontier Institutes of Life Science, and Science and Technology Xi'an Jiaotong University Xian Shanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle University of Toronto Center for the study of Pain Toronto Ontario Canada"},{"name":"Center for Neuron and Disease Frontier Institutes of Life Science, and Science and Technology Xi'an Jiaotong University Xian Shanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,7,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.152256"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4737-03.2004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/eujp.1999.0158"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/40645"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143808"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2010.09.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2862-07.2007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00206.2012"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-5-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00271-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094804"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2132313100"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.6.3004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1950"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.023"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.2.616"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1249-07.2007"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1760-08.2008"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1207"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00059.2001"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10849.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4059-04.2005"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-47"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05485.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00070.2006"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1118"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/16469"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191792"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90482.2008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.10.099"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.10.018"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020559"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5328.968"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0716-08.2008"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.025"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-20-08003.1997"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.122.3167.469"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.08.002"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00050.2005"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-15-06176.2003"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06029"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174868"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-1-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1704"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20512"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001269"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/83993"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00091.2005"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20331"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1812-08.2008"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1989.62.1.96"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.3"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.01.003"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12351","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12351","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.12351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T17:20:59Z","timestamp":1696267259000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.12351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,19]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1111\/jnc.12351"],"URL":"https:\/\/doi.org\/10.1111\/jnc.12351","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,19]]}}}