{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:05:50Z","timestamp":1790780750275,"version":"4.1.0"},"reference-count":71,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Itch-producing compounds stimulate receptors expressed on small diameter fibers that innervate the skin. Many of the currently known pruritogen receptors are G<jats:sub>q<\/jats:sub>Protein-Coupled Receptors (G<jats:sub>q<\/jats:sub>PCR), which activate Protein Kinase C (PKC). Specific isoforms of PKC have been previously shown to perform selective functions; however, the roles of PKC isoforms in regulating itch remain unclear. In this study, we investigated the novel PKC isoform PKC\u03b4 as an intracellular modulator of itch signaling in response to histamine and the non-histaminergic pruritogens chloroquine and \u03b2-alanine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Behavioral experiments indicate that PKC\u03b4 knock-out (KO) mice have a 40% reduction in histamine-induced scratching when compared to their wild type littermates. On the other hand, there were no differences between the two groups in scratching induced by the MRGPR agonists chloroquine or \u03b2-alanine. PKC\u03b4 was present in small diameter dorsal root ganglion (DRG) neurons. Of PKC\u03b4-expressing neurons, 55% also stained for the non-peptidergic marker IB4, while a smaller percentage (15%) expressed the peptidergic marker CGRP. Twenty-nine percent of PKC\u03b4-expressing neurons also expressed TRPV1. Calcium imaging studies of acutely dissociated DRG neurons from PKC\u03b4-KO mice show a 40% reduction in the total number of neurons responsive to histamine. In contrast, there was no difference in the number of capsaicin-responsive neurons between KO and WT animals. Acute pharmacological inhibition of PKC\u03b4 with an isoform-specific peptide inhibitor (\u03b4V1-1) also significantly reduced the number of histamine-responsive sensory neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that PKC\u03b4 plays a role in mediating histamine-induced itch, but may be dispensable for chloroquine- and \u03b2-alanine-induced itch.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-11-1","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T07:26:50Z","timestamp":1434612410000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Protein Kinase C\u03b4 Mediates Histamine-Evoked Itch and Responses in Pruriceptors"],"prefix":"10.1177","volume":"11","author":[{"given":"Manouela V","family":"Valtcheva","sequence":"first","affiliation":[{"name":"Washington University Pain Center and Department of Anesthesiology, Washington University in St. Louis, 660 S. Euclid Ave, Box 8054, 63110 St. Louis, MO, USA"},{"name":"Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Davidson","sequence":"additional","affiliation":[{"name":"Washington University Pain Center and Department of Anesthesiology, Washington University in St. Louis, 660 S. Euclid Ave, Box 8054, 63110 St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengshui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Washington University Pain Center and Department of Anesthesiology, Washington University in St. Louis, 660 S. Euclid Ave, Box 8054, 63110 St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leitges","sequence":"additional","affiliation":[{"name":"Biotechnology Centre of Oslo, University of Oslo, Blindern N-0317, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"Robert W","family":"Gereau","sequence":"additional","affiliation":[{"name":"Washington University Pain Center and Department of Anesthesiology, Washington University in St. Louis, 660 S. 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