{"id":253,"date":"2013-01-25T11:27:26","date_gmt":"2013-01-25T02:27:26","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=253"},"modified":"2013-07-17T01:28:34","modified_gmt":"2013-07-16T16:28:34","slug":"journal","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=253","title":{"rendered":"Journal club 2013-01-25"},"content":{"rendered":"

1744-8069-8-75<\/a><\/p>\n

\n

Mol Pain.<\/a>\u00a02012 Sep 27;8:75. doi: 10.1186\/1744-8069-8-75.<\/p>\n

Prostaglandin metabolite induces inhibition of TRPA1 and channel-dependent nociception.<\/h1>\n
Weng Y<\/a>,\u00a0Batista-Schepman PA<\/a>,\u00a0Barabas ME<\/a>,\u00a0Harris EQ<\/a>,\u00a0Dinsmore TB<\/a>,\u00a0Kossyreva EA<\/a>,\u00a0Foshage AM<\/a>,\u00a0Wang MH<\/a>,\u00a0Schwab MJ<\/a>,\u00a0Wang VM<\/a>,\u00a0Stucky CL<\/a>,\u00a0Story GM<\/a>.<\/div>\n
\n

Source<\/h3>\n

Department of Anesthesiology, Washington University Pain Center, St, Louis, MO 63110, USA. storyg@wustl.edu.<\/p>\n<\/div>\n

\n

ABSTRACT:<\/h3>\n

BACKGROUND:<\/h4>\n

The Transient Receptor Potential (TRP) ion channel TRPA1 is a key player in pain pathways. Irritant chemicals activate ion channel TRPA1 via covalent modification of N-terminal cysteines. We and others have shown that 15-Deoxy-\u039412, 14-prostaglandin J2 (15d-PGJ2) similarly activates TRPA1 and causes channel-dependent nociception. Paradoxically, 15d-PGJ2 can also be anti-nociceptive in several pain models. Here we hypothesized that activation and subsequent desensitization of TRPA1 in dorsal root ganglion (DRG) neurons underlies the anti-nociceptive property of 15d-PGJ2. To investigate this, we utilized a battery of behavioral assays and intracellular Ca2+ imaging in DRG neurons to test if pre-treatment with 15d-PGJ2 inhibited TRPA1 to subsequent stimulation.<\/p>\n

RESULTS:<\/h4>\n

Intraplantar pre-injection of 15d-PGJ2, in contrast to mustard oil (AITC), attenuated acute nocifensive responses to subsequent injections of 15d-PGJ2 and AITC, but not capsaicin (CAP). Intraplantar 15d-PGJ2-administered after the induction of inflammation-reduced mechanical hypersensitivity in the Complete Freund’s Adjuvant (CFA) model for up to 2\u2009h post-injection. The 15d-PGJ2-mediated reduction in mechanical hypersensitivity is dependent on TRPA1, as this effect was absent in TRPA1 knockout mice. Ca2+ imaging studies of DRG neurons demonstrated that 15d-PGJ2 pre-exposure reduced the magnitude and number of neuronal responses to AITC, but not CAP. AITC responses were not reduced when neurons were pre-exposed to 15d-PGJ2 combined with HC-030031 (TRPA1 antagonist), demonstrating that inhibitory effects of 15d-PGJ2 depend on TRPA1 activation. Single daily doses of 15d-PGJ2, administered during the course of 4\u2009days in the CFA model, effectively reversed mechanical hypersensitivity without apparent tolerance or toxicity.<\/p>\n

CONCLUSIONS:<\/h4>\n

Taken together, our data support the hypothesis that 15d-PGJ2 induces activation followed by persistent inhibition of TRPA1 channels in DRG sensory neurons in vitro and in vivo. Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics.<\/p>\n<\/div>\n

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

1744-8069-8-75 Mol Pain.\u00a02012 Sep 27;8:75. doi: 10.1186\/1744-8069-8-75. Prostaglandin metabolite induces inhibition of TRPA1 and channel-dependent nociception. Weng Y,\u00a0Batista-Schepman PA,\u00a0Barabas ME,\u00a0Harris EQ,\u00a0Dinsmore TB,\u00a0Kossyreva EA,\u00a0Foshage AM,\u00a0Wang MH,\u00a0Schwab MJ,\u00a0Wang VM,\u00a0Stucky CL,\u00a0Story GM. Source Department of Anesthesiology, Washington University Pain Center, St, Louis, MO 63110, USA. storyg@wustl.edu. ABSTRACT: BACKGROUND: The Transient Receptor Potential (TRP) ion channel TRPA1 is a […]<\/p>\n","protected":false},"author":3,"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\/253"}],"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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=253"}],"version-history":[{"count":5,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/253\/revisions"}],"predecessor-version":[{"id":257,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/253\/revisions\/257"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=253"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=253"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=253"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}