{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:52:28Z","timestamp":1774648348904,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07111"],"award-info":[{"award-number":["19K07111"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K09333"],"award-info":[{"award-number":["19K09333"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K09227"],"award-info":[{"award-number":["20K09227"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several lines of evidence have clarified that the key transmission pathways of itching sensation travel from the periphery to the central nervous system (CNS). Despite the functional significance of gastrin\u2010releasing peptide (GRP) and its cognate receptor in the itch processing mechanism in the spinal dorsal horn (SDH), the roles of GRP\u2010expressing (GRP<jats:sup>+<\/jats:sup>) neurons in different regions remain unclear. This study aimed to determine whether GRP<jats:sup>+<\/jats:sup> neurons in the CNS directly modulated itch processing. To specifically activate spinal and supraspinal GRP neurons by the designer receptors exclusively activated by designer drugs (DREADDs) system, CAG\u2010LSL\u2010Gq\u2010DREADD mice were crossed with GRP\u2010Cre mice, resulting in the development of GRP\u2010hM3Dq mice. Immunohistochemistry showed that hM3Dq was highly expressed in the SDH and brainstem closely related to sensory processing. The intraperitoneal, intrathecal, or intracerebroventricular administration of clozapine\u2010N\u2010oxide, an agonist of hM3Dq, strongly elicited dermatome\u2010dependent itch\u2010related scratching behavior, but did not change pain sensitivity. Importantly, GRP\u2010Gq\u2010DREADD\u2010mediated scratching behavior in GRP\u2010hM3Dq mice was not affected by the ablation of transient receptor potential vanilloid 1<jats:sup>+<\/jats:sup> sensory C\u2010fibers, and it was also observed to a similar degree under chronic itch conditions. Furthermore, there were no significant sex differences in the scratching behavior elicited by GRP\u2010Gq\u2010DREADD, suggesting that itch\u2010dominant roles of central GRP<jats:sup>+<\/jats:sup> neurons might be common in both sexes, at least under normal physiological conditions. These novel findings not only contribute to understanding the functional roles of central GRP<jats:sup>+<\/jats:sup> neurons further, but also propose the development of future effective therapeutics for intractable itching.<\/jats:p>","DOI":"10.1002\/prp2.790","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T17:36:30Z","timestamp":1621272990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chemogenetic activation of central gastrin\u2010releasing peptide\u2010expressing neurons elicits itch\u2010related scratching behavior in male and female mice"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5401-8650","authenticated-orcid":false,"given":"Norikazu","family":"Kiguchi","sequence":"first","affiliation":[{"name":"Department of Pharmacology Wakayama Medical University Wakayama City Wakayama Japan"},{"name":"Department of Physiological Sciences School of Pharmaceutical Sciences Wakayama Medical University Wakayama City Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohji","family":"Fukazawa","sequence":"additional","affiliation":[{"name":"Department of Anatomy Kansai University of Health Sciences Sennan\u2010gun Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Saika","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wakayama Medical University Wakayama City Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Uta","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacology Faculty of Pharmaceutical Sciences University of Toyama Toyama City Toyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiro","family":"Saika","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wakayama Medical University Wakayama City Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoe Y.","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wakayama Medical University Wakayama City Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Chuan","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Wake Forest University School of Medicine Winston\u2010Salem NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiroh","family":"Kishioka","sequence":"additional","affiliation":[{"name":"Faculty of Wakayama Health Care Sciences Takarazuka University of Medical and Health Care Wakayama City Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.446"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1208814"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3343"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.03.023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.09.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3619"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201603042"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3289"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3881"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.07.035"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16859-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2017.08.010"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.229997"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11676"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108025"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174868"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70528"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916643724"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06029"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916649602"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-79"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0141-1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15230-y"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067422"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.07.033"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13199"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/npr2.12120"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000097"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1133-5"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14747"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2559-18.2019"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.09.011"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52642-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-47"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.04.022"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.01.016"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90860-K"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.178970"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.07.038"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0012-1"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113320"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23506"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000861"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aak9748"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31561-0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08475-9"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-777"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.12.001"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(97)00199-1"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00925"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4053"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.06.016"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194660"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000389"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.790","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.790","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:46:17Z","timestamp":1693205177000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/prp2.790"],"URL":"https:\/\/doi.org\/10.1002\/prp2.790","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"2021-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00790"}}