MP28-12 EFFECT OF A BIFUNCTIONAL MU/DELTA OPIOID RECEPTOR LIGAND ON MECHANOSENSITIVE PELVIC NERVE AFFERENT FIBERS INNERVATING THE URINARY BLADDER OF RATS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I (MP28)1 Apr 2020MP28-12 EFFECT OF A BIFUNCTIONAL MU/DELTA OPIOID RECEPTOR LIGAND ON MECHANOSENSITIVE PELVIC NERVE AFFERENT FIBERS INNERVATING THE URINARY BLADDER OF RATS Maia Terashvili*, Pradeep Kannampalli, Bidyut K. Medda, Banani Banerjee, Christopher W. Cunningham, and Jyoti N. Sengupta Maia Terashvili*Maia Terashvili* More articles by this author , Pradeep KannampalliPradeep Kannampalli More articles by this author , Bidyut K. MeddaBidyut K. Medda More articles by this author , Banani BanerjeeBanani Banerjee More articles by this author , Christopher W. CunninghamChristopher W. Cunningham More articles by this author , and Jyoti N. SenguptaJyoti N. Sengupta More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000867.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial cystitis/painful bladder syndrome (IC/PBS) affects about 3-8 million women and 1-4 million men in the United States. There is an immediate need to develop medications that can effectively manage the severity of pain associated with IC/PBS. The conventional opioid therapy like morphine and its derivatives carry multiple adverse effects including tolerance, addiction, constipation and dependence. A bifunctional opioid ligand acts on two opioid receptors, but does not produce adverse CNS effects. This study investigates the analgesic effect of benzylideneoxymorphone (BOM), a bifunctional partial opioid ligand, which acts as partial agonist for mu-opioid receptors (MORs) and antagonist for delta-opioid receptors (DORs), in a rat model of cystitis-induced bladder pain. Due to unique pharmacological profile of BOM, we hypothesized that this compound would be effective in managing pain in IC/PBS patients without producing adverse CNS effects. METHODS: In our study, Inflammation was induced in female rats by intravesical administration of zymosan (5% in saline) for 3 days. On day 5, we investigated the inhibitory effect of different doses (1, 5 and 10mg/Kg, i.v.) of BOM on the responses of urinary bladder distension (UBD)-sensitive pelvic nerve afferent (PNA) fibers during bladder distension of non-inflamed naïve and cystitis rats. In addition, MORs expression in the lumbo-sacral (L6-S1) spinal cord was evaluated in Western Blot analysis experiments. RESULTS: The drug produced a dose-dependent inhibition of responses of UBD-sensitive PNA fibers in the lumbar 6 (L6) dorsal root from zymosan-induced cystitis rats. In contrast, in naïve non-inflamed rats BOM did not produce inhibition of responses of UBD-sensitive PNA afferents fibers. The Western Blot analysis of tissues from L6-S1 spinal cord exhibited marked upregulation of MORs protein expression of tissues from cystitis rats compared to that of non-inflamed naïve rats. CONCLUSIONS: These results indicate that BOM attenuates responses of UBD-sensitive PNA fibers of cystitis rats in contrast to non-inflamed rats, which could be due to altered expressions of MOR in the bladder innervating PNA afferent fibers. Therefore, BOM could be a leading compound as analgesic drug to manage pain associated with IC/PBS. In addition, the drug can be promising to manage chronic pelvic pain without adverse CNS effects. Source of Funding: NIH R01DK099201 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e424-e424 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maia Terashvili* More articles by this author Pradeep Kannampalli More articles by this author Bidyut K. Medda More articles by this author Banani Banerjee More articles by this author Christopher W. Cunningham More articles by this author Jyoti N. Sengupta More articles by this author Expand All Advertisement PDF downloadLoading ...