MP39-06 PELVIC PAIN MODULATION AND TARGETING THROUGH ARACHIDONIC ACID METABOLISM

Abstract

Listen

Translate article

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2018MP39-06 PELVIC PAIN MODULATION AND TARGETING THROUGH ARACHIDONIC ACID METABOLISM Wenbin Yang, Ryan Yaggie, Charles Rudick, Anthony Schaeffer, and David Klumpp Wenbin YangWenbin Yang More articles by this author , Ryan YaggieRyan Yaggie More articles by this author , Charles RudickCharles Rudick More articles by this author , Anthony SchaefferAnthony Schaeffer More articles by this author , and David KlumppDavid Klumpp More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1253AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/bladder pain syndrome (IC) is a debilitating condition of chronic pelvic pain and urinary dysfunction. Using a murine neurogenic cystitis model that recapitulates key aspects of IC, we recently identified acyloxyacyl hydrolase (AOAH) as a novel modulator of pelvic pain. Here we show that AOAH modulates pain severity by mediating arachidonic acid homeostasis and metabolism and identifies novel therapeutic target for chronic pelvic pain. METHODS Metabolite analysis: Metabolites was extracted from mouse sacral spinal cord, then separated by reverse-phase liquid chromatography (LC) on a C18 column. All MS analyses were performed using QTRAP 6500 and operated in multiple reaction monitoring (MRM) mode. Eicosanoids were detected in negative electrospray ion mode and endocannabinoids detected in positive ion mode. Metabolites were quantified by measuring the area under the peak relative to internal standards. RESULTS Homology with lecithin-cholesterol acyltransferase suggested that AOAH mediates transfer of arachidonic acid between phospholipids. Spinal cord lipidomics revealed increased arachidonic acid-containing phosphatidylcholine in AOAH-deficient mice and concomitantly decreased phosphatidylethanolamine, consistent with loss of arachidonyl transferase activity. In spinal cords, AOAH deficiency was also associated with elevated arachidonic acid and PGE2, and pelvic pain was reduced in AOAH-deficient mice by a PGE2 receptor antagonist. CONCLUSIONS These findings suggest that AOAH modulates pelvic pain pathways at the level of arachidonic acid homeostasis. Furthermore, arachidonic acid metabolism offers new therapeutic targets for treating chronic pelvic pain. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e511-e512 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Wenbin Yang More articles by this author Ryan Yaggie More articles by this author Charles Rudick More articles by this author Anthony Schaeffer More articles by this author David Klumpp More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...