{"id":1301,"date":"2016-09-23T10:09:54","date_gmt":"2016-09-23T01:09:54","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1301"},"modified":"2016-09-23T10:11:01","modified_gmt":"2016-09-23T01:11:01","slug":"journal-club-2016-9-23","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1301","title":{"rendered":"Journal Club 2016.9.23"},"content":{"rendered":"

The Cancer<\/span> Chemotherapeutic<\/span> Paclitaxel<\/span> Increases<\/span> Human<\/span> and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4.<\/h1>\n
Li Y<\/span><\/a>1<\/span><\/sup>, Adamek P<\/span><\/a>2<\/span><\/sup>, Zhang H<\/span><\/a>3<\/span><\/sup>, Tatsui CE<\/span><\/a>4<\/span><\/sup>, Rhines LD<\/span><\/a>4<\/span><\/sup>, Mrozkova P<\/span><\/a>2<\/span><\/sup>, Li Q<\/span><\/a>5<\/span><\/sup>, Kosturakis AK<\/span><\/a>6<\/span><\/sup>, Cassidy RM<\/span><\/a>7<\/span><\/sup>, Harrison DS<\/span><\/a>8<\/span><\/sup>, Cata JP<\/span><\/a>5<\/span><\/sup>, Sapire K<\/span><\/a>5<\/span><\/sup>, Zhang H<\/span><\/a>1<\/span><\/sup>, Kennamer-Chapman RM<\/span><\/a>7<\/span><\/sup>, Jawad AB<\/span><\/a>7<\/span><\/sup>, Ghetti A<\/span><\/a>9<\/span><\/sup>, Yan J<\/span><\/a>5<\/span><\/sup>, Palecek J<\/span><\/a>2<\/span><\/sup>, Dougherty PM<\/span><\/a>10<\/span><\/sup>.<\/div>\n
\n

Abstract<\/h3>\n
\n

Peripheral neuropathy is dose limiting in paclitaxel<\/span> cancer<\/span> chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer<\/span> survivors. The hypothesis tested was that paclitaxel<\/span> produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel<\/span>-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1(+) neurons is increased in the dorsal root ganglia (DRG) in paclitaxel<\/span>-treated rats and is colocalized with TLR4 in rat and human<\/span> DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1(+) neurons by paclitaxel<\/span> treatment. Perfusion of paclitaxel<\/span> or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel<\/span> and LPS sensitize TRPV1 in HEK293 cells stably expressing human<\/span> TLR4 and transiently expressing human<\/span> TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel<\/span> activates and sensitizes TRPV1 responses directly in dissociated human<\/span> DRG neurons. In summary, TLR4 was activated by paclitaxel<\/span> and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel<\/span>-induced acute pain and chronic painful neuropathy. Significance statement: In this original work, it is shown for the first time that paclitaxel<\/span> activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human<\/span> dorsal root ganglion neurons, TLR4\/TRPV1-coexpressing HEK293 cells, and in both rat and mouse spinal cord slices. Moreover, this is the first study to show that this interaction plays an important role in the generation of behavioral hypersensitivity in paclitaxel<\/span>-related neuropathy. The key translational implications are that TLR4 and TRPV1 antagonists may be useful in the prevention and treatment of chemotherapy-induced peripheral neuropathy in humans<\/span>.<\/p>\n

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4. Li Y1, Adamek P2, Zhang H3, Tatsui CE4, Rhines LD4, Mrozkova P2, Li Q5, Kosturakis AK6, Cassidy RM7, Harrison DS8, Cata JP5, Sapire K5, Zhang H1, Kennamer-Chapman RM7, Jawad AB7, Ghetti A9, Yan J5, Palecek J2, Dougherty PM10. […]<\/p>\n","protected":false},"author":5,"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\/1301"}],"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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1301"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1301\/revisions"}],"predecessor-version":[{"id":1303,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1301\/revisions\/1303"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1301"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1301"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1301"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}