{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:37:10Z","timestamp":1790487430445,"version":"4.1.0"},"reference-count":30,"publisher":"American Physiological Society","issue":"1","funder":[{"name":"NIH","award":["NS047399"],"award-info":[{"award-number":["NS047399"]}]},{"name":"NIH","award":["NS014624"],"award-info":[{"award-number":["NS014624"]}]},{"name":"Johns  Hopkins Blaustin Pain Research Grant","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:p> Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10\/CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS. This current was modulated by intracellular Cl<jats:sup>\u2212<\/jats:sup> and blocked by the general Cl<jats:sup>\u2212<\/jats:sup> channel inhibitors. Moreover, increasing Ca<jats:sup>2+<\/jats:sup> buffering capacity reduced this current. In addition, blockade of Cl<jats:sup>\u2212<\/jats:sup> channels significantly suppressed CXCL10-induced Ca<jats:sup>2+<\/jats:sup> response. In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10 were attenuated by either of two Cl<jats:sup>\u2212<\/jats:sup> channel blockers. Thus we suggest that the Cl<jats:sup>\u2212<\/jats:sup> channel acts as a downstream target mediating the excitatory and pruritic behavioral effects of CXCL10. Cl<jats:sup>\u2212<\/jats:sup> channels may provide a promising therapeutic target for the treatment of allergic itch in which CXCL10\/CXCR3 signaling may participate. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY The ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch are largely unexplored. This study revealed that CXCL10 evoked an ionic current mainly carried by Cl<jats:sup>\u2212<\/jats:sup> channels. We suggest that Cl<jats:sup>\u2212<\/jats:sup> channels are likely key molecular candidates responsible for the CXCL10-evoked neuronal activation and itch-like behaviors in a murine model of allergic contact dermatitis induced by the antigen squaric acid dibutylester. Cl<jats:sup>\u2212<\/jats:sup> channels may emerge as a promising drug target for the treatment of allergic itch in which CXCL10\/CXCR3 signaling may participate. <\/jats:p>","DOI":"10.1152\/jn.00187.2017","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T20:50:27Z","timestamp":1493239827000},"page":"619-624","source":"Crossref","is-referenced-by-count":19,"title":["Cl<sup>\u2212<\/sup> channel is required for CXCL10-induced neuronal activation and itch response in a murine model of allergic contact dermatitis"],"prefix":"10.1152","volume":"118","author":[{"given":"Lintao","family":"Qu","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, Maryland; and"},{"name":"Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"LaMotte","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-38"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1312-09.2009"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.01995.x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3111"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/s12990-015-0061-y"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3195"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135811"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.4.1398"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00730.x"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.01.001"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.03.062"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-32"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.07.011"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63986-7"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01186-9"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.032003.154341"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25823"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41084"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0300-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00970.2011"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s12990-015-0042-1"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu007"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000208"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6355-11.2012"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.04.008"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3221"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01007.2007"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040779"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(01)00172-4"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2789"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00187.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T02:24:24Z","timestamp":1567995864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00187.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,1]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,7,1]]}},"alternative-id":["10.1152\/jn.00187.2017"],"URL":"https:\/\/doi.org\/10.1152\/jn.00187.2017","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,1]]}}}