{"id":147,"date":"2012-09-27T10:49:12","date_gmt":"2012-09-27T01:49:12","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=147"},"modified":"2012-09-27T10:50:35","modified_gmt":"2012-09-27T01:50:35","slug":"2012-09-20-journal-club","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=147","title":{"rendered":"Journal club 2012-09-20"},"content":{"rendered":"

JCI45414<\/a>\u00a0 \u00a0\u00a0JCI45414sd<\/a><\/p>\n

J Clin Invest. 2012 Jun 1;122(6):2195-207. doi: 10.1172\/JCI45414. Epub 2012 May\u00a08.<\/p>\n

TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization,\u00a0and pruritus in mice.<\/strong><\/p>\n

Liu T, Berta T, Xu ZZ, Park CK, Zhang L, L\u00fc N, Liu Q, Liu Y, Gao YJ, Liu YC, Ma
\nQ, Dong X, Ji RR.<\/p>\n

Sensory Plasticity Laboratory, Pain Research Center, Department of
\nAnesthesiology, Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital and\u00a0Harvard Medical School, Boston, Massachusetts, USA.<\/p>\n

Itch, also known as pruritus, is a common, intractable symptom of several skin\u00a0diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and\u00a0regulate neuropathic pain, but their roles in pruritus are elusive. Here, we\u00a0report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed\u00a0mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs)\u00a0that coexpress the itch signaling pathway components transient receptor potential\u00a0subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a\u00a0TLR3 agonist induces inward currents and action potentials in DRG neurons and\u00a0elicited scratching in WT mice but not Tlr3(-\/-) mice. Furthermore, excitatory\u00a0synaptic transmission in spinal cord slices and long-term potentiation in the\u00a0intact spinal cord were impaired in Tlr3(-\/-) mice but not Tlr7(-\/-) mice.\u00a0Consequently, central sensitization-driven pain hypersensitivity, but not acute\u00a0pain, was impaired in Tlr3(-\/-) mice. In addition, TLR3 knockdown in DRGs also\u00a0attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was\u00a0substantially reduced in Tlr3(-\/-) mice. Our findings demonstrate a critical role\u00a0of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic\u00a0transmission, and central sensitization. TLR3 may serve as a new target for\u00a0developing anti-itch treatment.<\/p>\n

PMCID: PMC3366391
\nPMID: 22565312 [PubMed – indexed for MEDLINE]<\/p>\n

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

JCI45414\u00a0 \u00a0\u00a0JCI45414sd J Clin Invest. 2012 Jun 1;122(6):2195-207. doi: 10.1172\/JCI45414. Epub 2012 May\u00a08. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization,\u00a0and pruritus in mice. Liu T, Berta T, Xu ZZ, Park CK, Zhang L, L\u00fc N, Liu Q, Liu Y, Gao YJ, Liu YC, Ma Q, Dong X, Ji RR. Sensory Plasticity Laboratory, Pain […]<\/p>\n","protected":false},"author":1,"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\/147"}],"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\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=147"}],"version-history":[{"count":7,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/147\/revisions"}],"predecessor-version":[{"id":154,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/147\/revisions\/154"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=147"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=147"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=147"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}