{"id":1905,"date":"2020-03-16T17:50:00","date_gmt":"2020-03-16T08:50:00","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1905"},"modified":"2020-03-16T17:53:52","modified_gmt":"2020-03-16T08:53:52","slug":"2020-03-19","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1905","title":{"rendered":"2020.03.19"},"content":{"rendered":"\n

Complementary roles of murine NaV<\/sub>1.7, NaV<\/sub>1.8 and NaV<\/sub>1.9 in acute itch signalling<\/h1>\n\n\n\n

Helen K\u00fchn<\/a>*, Leonie Kappes<\/a>, Katharina Wolf<\/a>, Lisa Gebhardt<\/a>, Markus F. Neurath<\/a>, Peter Reeh<\/a>, Michael J. M. Fischer<\/a> & Andreas E. Kremer<\/a>* <\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

Acute pruritus occurs in various disorders. Despite severe repercussions on quality of life treatment options remain limited. Voltage-gated sodium channels (NaV<\/sub>) are indispensable for transformation and propagation of sensory signals implicating them as drug targets. Here, NaV<\/sub>1.7, 1.8 and 1.9 were compared for their contribution to itch by analysing NaV<\/sub>-specific knockout mice. Acute pruritus was induced by a comprehensive panel of pruritogens (C48\/80, endothelin, 5-HT, chloroquine, histamine, lysophosphatidic acid, trypsin, SLIGRL, \u03b2-alanine, BAM8-22), and scratching was assessed using a magnet-based recording technology. We report an unexpected stimulus-dependent diversity in NaV<\/sub> channel-mediated itch signalling. NaV<\/sub>1.7\u2212\/\u2212<\/sup> showed substantial scratch reduction mainly towards strong pruritogens. NaV<\/sub>1.8\u2212\/\u2212<\/sup> impaired histamine and 5-HT-induced scratching while NaV<\/sub>1.9 was involved in itch signalling towards 5-HT, C48\/80 and SLIGRL. Furthermore, similar microfluorimetric calcium responses of sensory neurons and expression of itch-related TRP channels suggest no change in sensory transduction but in action potential transformation and conduction. The cumulative sum of scratching over all pruritogens confirmed a leading role of NaV<\/sub>1.7 and indicated an overall contribution of NaV<\/sub>1.9. Beside the proposed general role of NaV<\/sub>1.7 and 1.9 in itch signalling, scrutiny of time courses suggested NaV<\/sub>1.8 to sustain prolonged itching. Therefore, NaV<\/sub>1.7 and 1.9 may represent targets in pruritus therapy.<\/p>\n\n\n\n

Complementary-roles-of-murine-voltage-gated-sodium-channels-1.7-1.8-1.9-in-acute-itch-signalling-<\/a>Download<\/a><\/div>\n\n\n\n
Supplementary-Information<\/a>Download<\/a><\/div>\n\n\n\n

<\/p>\n\n\n\n

<\/h2>\n","protected":false},"excerpt":{"rendered":"

Complementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signalling Helen K\u00fchn*, Leonie Kappes, Katharina Wolf, Lisa Gebhardt, Markus F. Neurath, Peter Reeh, Michael J. M. Fischer & Andreas E. Kremer*  Abstract Acute pruritus occurs in various disorders. Despite severe repercussions on quality of life treatment options remain limited. Voltage-gated sodium channels (NaV) are indispensable for transformation and propagation of sensory […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1905"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1905"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1905\/revisions"}],"predecessor-version":[{"id":1909,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1905\/revisions\/1909"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1905"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1905"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1905"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}