You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II (PD24)1 Apr 2020PD24-06 MOLECULAR ALTERATION OF GABAERGIC PAIN MODULATORY PATHWAY IN THE ROSTRAL VENTROMEDIAL MEDULLA FOLLOWING ZYMOSAN-INDUCED CYSTITIS IN RATS Bidyut K. Medda*, Sankar Addya, Bhavana Talluri, Faith Hoelzel, Maia Terashvili, Patrick Sanvanson, Reza Shaker, Jyoti N. Sengupta, and Banani Banerjee Bidyut K. Medda*Bidyut K. Medda* More articles by this author , Sankar AddyaSankar Addya More articles by this author , Bhavana TalluriBhavana Talluri More articles by this author , Faith HoelzelFaith Hoelzel More articles by this author , Maia TerashviliMaia Terashvili More articles by this author , Patrick SanvansonPatrick Sanvanson More articles by this author , Reza ShakerReza Shaker More articles by this author , Jyoti N. SenguptaJyoti N. Sengupta More articles by this author , and Banani BanerjeeBanani Banerjee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000881.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The rostral ventromedial medulla (RVM) comprises of several subsets of neurons, which send descending projections to the spinal cord to modulate pain. These neurons are the major targets of efferent projections from the periaqueductal gray (PAG), the site of action of opioid-mediated analgesia. The majority of RVM originating descending neurons are GABAergic. Recently, we have documented microRNA (miRNA)-mediated transcriptional deregulation of spinal GABAergic system and visceral hypersensitivity (colon and bladder) in rats with zymosan-induced cystitis. The objective was to study the effect of noxious bladder insult on molecular expression of GABAergic RVM neurons of rats with zymosan-induced cystitis. METHODS: Two groups of Sprague Dawley rats (n=8 /group) were used in this study. Experimental and control groups received transurethral zymosan (1% in saline, 300ul) and saline respectively for 3 days from postnatal (P) days P58 through P60. Rats in both groups were euthanized on P60 and RVM tissues were collected for analysis. Gene expression profiles of experimental and control groups were evaluated using Rat Clariton S transcriptome arrays. miRNA expression profiles were examine using Affymatrix Gene Chips miRNA arrays. Individual gene was further evaluated using immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: Intravesical zymosan treatment resulted in 4-fold downregulation of GABAA receptor subunit alpha 6 (GABAAα6) and glycine transporter Gly 2 (p<0.05 vs controls). Fourteen miRNAs demonstrated differential expression in zymosan treated rats (p<0.05 vs controls). The target gene prediction identified two upregulated miRNAs; miR-129-5p and miR-300 with complementary binding sites for 3’UTRs of GABAAα6 gene indicating a possible post-transcriptional deregulation of the RVM GABAergic pathway in zymosan-treated cystitis rats. A significant downregulation of RVM vesicular GABA transporter VGAT expression was observed in cystitis group by ISH (p<0.05 vs controls). The expression profile of GABAAα6 in RVM was validated by IHC. CONCLUSIONS: Cystitis results in miRNA-mediated transcriptional deregulation of GABA receptor and transporter expression in RVM neurons. This finding strongly suggests that the suppression of the RVM inhibitory transmission may contribute towards the development of spinal neuron hyperexcitability and bladder pain. Source of Funding: NIH R01DK099201 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e534-e534 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bidyut K. Medda* More articles by this author Sankar Addya More articles by this author Bhavana Talluri More articles by this author Faith Hoelzel More articles by this author Maia Terashvili More articles by this author Patrick Sanvanson More articles by this author Reza Shaker More articles by this author Jyoti N. Sengupta More articles by this author Banani Banerjee More articles by this author Expand All Advertisement PDF downloadLoading ...