{"id":3583,"date":"2025-11-03T10:46:31","date_gmt":"2025-11-03T01:46:31","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3583"},"modified":"2025-11-03T10:47:09","modified_gmt":"2025-11-03T01:47:09","slug":"journal-club-25-11-03","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3583","title":{"rendered":"Journal Club 25-11-03"},"content":{"rendered":"\n

Keratinocyte\u2013TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch<\/h1>\n\n\n\n

Andrew J. Crowther<\/a> https:\/\/orcid.org\/0000-0001-9269-6188<\/a>, Sakeen W. Kashem<\/a>, Madison E. Jewell<\/a> https:\/\/orcid.org\/0009-0004-8337-1583<\/a>, +8 , and Allan I. Basbaum<\/a> https:\/\/orcid.org\/0000-0002-1710-6333<\/a> allan.basbaum@ucsf.edu<\/a>Authors Info & Affiliations<\/a><\/p>\n\n\n\n

Edited by Peter Strick, University of Pittsburgh Brain Institute, Pittsburgh, PA; received June 13, 2024; accepted May 5, 2025<\/p>\n\n\n\n

June 11, 2025<\/strong>, 122 (24) e2411724122, https:\/\/doi.org\/10.1073\/pnas.2411724122<\/p>\n\n\n\n

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

Our understanding of neural circuits that respond to skin dysfunction, triggering itch, and pathophysiological scratching remains incomplete. Here, we describe a profound chronic itch phenotype in transgenic mice expressing the tetracycline transactivator (tTA) gene within the Phox2a lineage. Phox2a; tTA mice exhibit intense, localized scratching and regional skin lesions, controllable by the tTA inhibitor, doxycycline. As gabapentin and the kappa opioid receptor agonist, nalfurafine, but not morphine, significantly reduce scratching, this phenotype has a pharmacological profile of neuropathic pruritus. Importantly, the Phox2a; tTA expression occurs in a spatially restricted population of skin keratinocytes that overlaps precisely with the skin area that is scratched. Localized Gi<\/sub>-DREADD-mediated inactivation of these Phox2a-keratinocytes completely reverses the skin lesions, while inducible tTA activation of keratinocytes initiates the condition. Notably, ablation of TRPV1-expressing primary afferent neurons also reduces scratching and skin lesions, but this occurs slowly, over a course of two months. In contrast denervation induced loss of all cutaneous input rapidly blocks scratching. These findings identify the cellular, molecular, and topographic basis of a robust and chronic sensory neuron\u2013dependent and gabapentin-responsive neuropathic itch that is initiated by genetic factors within keratinocytes.<\/p>\n\n\n\n

<\/object>Keratinocyte\u2013TRPV1-sensory-neuron-interactions-in-a-genetically-controllable-mouse-model-of-chronic-neuropathic-itch<\/a>Download<\/a><\/div>\n\n\n\n
<\/object>pnas.2411724122.sapp_<\/a>Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"

Keratinocyte\u2013TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch Andrew J. Crowther https:\/\/orcid.org\/0000-0001-9269-6188, Sakeen W. Kashem, Madison E. Jewell https:\/\/orcid.org\/0009-0004-8337-1583, +8 , and Allan I. Basbaum https:\/\/orcid.org\/0000-0002-1710-6333 allan.basbaum@ucsf.eduAuthors Info & Affiliations Edited by Peter Strick, University of Pittsburgh Brain Institute, Pittsburgh, PA; received June 13, 2024; accepted May 5, 2025 June 11, 2025, 122 (24) e2411724122, https:\/\/doi.org\/10.1073\/pnas.2411724122 Abstract Our understanding of neural circuits that respond […]<\/p>\n","protected":false},"author":2,"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\/3583"}],"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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3583"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3583\/revisions"}],"predecessor-version":[{"id":3587,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3583\/revisions\/3587"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3583"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3583"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3583"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}