TRPV4 ROLE IN VISCERAL HYPERSENSITIVITY<\/a><\/p>\nNICOLAS CENAC,*,\u2021,\u00a7 CHRISTOPHE ALTIER,* KEVIN CHAPMAN,* WOLFGANG LIEDTKE, GERALD ZAMPONI,* and NATHALIE VERGNOLLE*,\u2021,\u00a7
\n*Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada; \u2021INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; \u00a7Universit\u00e9 Toulouse III Paul Sabatier, Toulouse, France; and Center for Translational Neuroscience, Duke University Medical Center, Durham, North Carolina<\/p>\n
Background & Aims: The transient receptor potential vanilloid-4 (TRPV4) is an osmosensitive channel that responds to mechanical stimulation. We hypothesized that TRPV4 could be important in visceral nociception and in the development of hypersensitivity. Methods: TRPV4 expression was investigated by immunohis- tochemistry and reverse transcription\u2013polymerase chain reaction. Calcium signaling and patch-clamp studies were performed in dorsal root ganglia (DRG) neurons validating the use of 4 PDD as a selective TRPV4 agonist. The effects of TRPV4 activation on visceral nociception were evaluated in mice that re- ceived intracolonically TRPV4 agonist (4 -phorbol 12,13-didecanoate [4 PDD]) and in TRPV4-deficient mice in which abdominal muscle contractions in re- sponse to colorectal distention (CRD) were recorded. Intervertebral injections of TRPV4 or mismatch small interfering RNA (siRNA) were used to specifically down-regulate TRPV4 expression in sensory neurons and to investigate the role of TRPV4 in basal visceral nociception or in protease-activated receptor 2 (PAR2) activation-induced visceral hypersensitivity. Results: TRPV4 agonist 4 PDD specifically activated a cat- ionic current and calcium influx in colonic projec- tions of DRG neurons and caused dose-dependent visceral hypersensitivity. TRPV4-targeted but not mismatched siRNA intervertebral treatments were ef- fective at reducing basal visceral nociception, as well as 4 PDD or PAR2 agonist-induced hypersensitivity. Effects of the TRPV4 ligand were lost in TRPV4- deficient mice. Conclusions: 4 PDD selectively acti- vates TRPV4 in sensory neurons projecting from the colon, and TRPV4 activation causes visceral hypersen- sitivity. TRPV4 activation is implicated in the nocicep- tive response to CRD in basal conditions and in PAR2 agonist-induced hypersensitivity. These results suggest a pivotal role for TRPV4 in visceral nociception and hypersensitivity.<\/p>\n","protected":false},"excerpt":{"rendered":"
Transient Receptor Potential Vanilloid-4 Has a Major Role in Visceral Hypersensitivity Symptoms TRPV4 ROLE IN VISCERAL HYPERSENSITIVITY NICOLAS CENAC,*,\u2021,\u00a7 CHRISTOPHE ALTIER,* KEVIN CHAPMAN,* WOLFGANG LIEDTKE, GERALD ZAMPONI,* and NATHALIE VERGNOLLE*,\u2021,\u00a7 *Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada; \u2021INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; \u00a7Universit\u00e9 Toulouse III Paul […]<\/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\/1610"}],"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=1610"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1610\/revisions"}],"predecessor-version":[{"id":1613,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1610\/revisions\/1613"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}