MP03-03 TRANSCRIPTOME ANALYSIS IN LUMBOSACRAL DORSAL ROOT GANGLIA REVEALS KEY MOLECULAR CHANGES IN ANIMAL MODELS OF UROLOGICAL CHRONIC PELVIC PAIN SYNDROME (UCPPS)

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP03-03 TRANSCRIPTOME ANALYSIS IN LUMBOSACRAL DORSAL ROOT GANGLIA REVEALS KEY MOLECULAR CHANGES IN ANIMAL MODELS OF UROLOGICAL CHRONIC PELVIC PAIN SYNDROME (UCPPS) Sathish Kumar Yesupatham and Alison Xiaoqiao Xie Sathish Kumar YesupathamSathish Kumar Yesupatham More articles by this author and Alison Xiaoqiao XieAlison Xiaoqiao Xie More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with UCPPS experience chronic pelvic pain and lower urinary tract symptoms (LUTS), such as urinary frequency, urgency, and nocturia. UCPPS symptoms are often associated with nociceptive sensitization in the peripheral and central nervous system, which underlies symptoms of bladder overactivity, pelvic pain, and centralized pain. Understanding the molecular mechanism underlying the pathogenesis of nociceptive sensitization is necessary for finding better drug targets and neuromodulation protocols to treat UCPPS symptoms. However, despite transcriptomic analysis has been conducted on the L4 & L5 dorsal root ganglia (DRGs) in injury-induced pain models, genomic analysis focusing on bladder sensory pathways have not been performed. The current study aims to characterize transcriptome changes in lumbosacral DRGs receiving bladder and pelvic sensory input in a mouse model of UCPPS. METHODS: Male and female C57BL6/J mice were used in this study. UCPPS symptoms was induced by intravesical instillations of recombinant mouse vascular endothelial growth factor (VEGFA), an animal mode of UCPPS we previously established. As a read-out of visceral hypersensitivity, Von Frey assay was performed and compared between VEGF-instilled experimental group and saline-instilled control group. Mice were sacrificed after VEGF-induced visceral hypersensitivity was observed, and their L1, L2, L6, S1 and S2 DRGs was harvested for bulk-RNA sequencing. RESULTS: Samples were sequenced at a depth of 40 million reads per sample. Data analysis was performed using Basepair Tech platform. Ingenuity pathway analysis (Qiagen) enabled to visualize the biological network changes due to UCPPS. Spliced Transcripts Alignment to a Reference (mm10) revealed changes in the Nociceptor signaling. Principal component analysis score confirms the global gene expression changes in UCPPS-like experimental group. Upstream analysis on VEGF signaling revealed activation/ inhibition of transcriptional factors like ATF3, FOSB, and BCL2. CONCLUSIONS: Our data is the first characterization on key signaling pathway changes in lumbosacral DRGs during the pathogenesis of UCPPS symptoms in animal models. VEGF and its receptors have been recognized as a urine biomarker for UCPPS in patients. Ongoing transcriptome analysis such as Ingenuity pathway analysis and Gene set enrichment analysis will further reveal the etiology of pain centric UCPPS. Source of Funding: NIDDK 25B0965/5R01DK129260-02 (Xie) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e22 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sathish Kumar Yesupatham More articles by this author Alison Xiaoqiao Xie More articles by this author Expand All Advertisement PDF downloadLoading ...