MP07-06 CHRONIC LL-37 INDUCED CYSTITIS PRODUCES PAIN INDEPENDENT OF INFLAMMATION AND MODIFIED GLYCOSAMINOGLYCANS ARE POTENT NON-OPIOID ANALGESICS

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (MP07)1 Apr 2020MP07-06 CHRONIC LL-37 INDUCED CYSTITIS PRODUCES PAIN INDEPENDENT OF INFLAMMATION AND MODIFIED GLYCOSAMINOGLYCANS ARE POTENT NON-OPIOID ANALGESICS Austin Schults*, Wanjian Jia, M. Martin Jensen, Glenn Prestwich, and Siam Oottamasathien Austin Schults*Austin Schults* More articles by this author , Wanjian JiaWanjian Jia More articles by this author , M. Martin JensenM. Martin Jensen More articles by this author , Glenn PrestwichGlenn Prestwich More articles by this author , and Siam OottamasathienSiam Oottamasathien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000827.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial cystitis/painful bladder syndrome (IC/PBS) can be a debilitating condition that dramatically impacts the quality of life for patients. The primary goal of patients with IC/PBS is to provide symptomatic relief. The immunomodulatory human cathelicidin (antimicrobial peptide) LL-37 induces profound acute bladder inflammation and pain. Our objectives were to evaluate a chronic pain profile associated with an LL-37-induced murine model of IC/PBS, along with the analgesic effects of modified glycosaminoglycan ether compounds. We hypothesized that chronic pain could be produced that is independent of inflammation and that a semi-synthetic glycosaminoglycan ether (SAGE GM-0111) could be a potent non-opioid analgesic in the setting of chronic LL-37-induced cystitis. METHODS: Bladder instillation of 150μL of 80 µM LL-37 for 1-hr, biweekly for four weeks induced the chronic IC/PBS model. SAGE analgesic effects were tested by instilling SAGE GM-0111. Pain responses to suprapubic stimulation were assessed using von Frey filaments (0.04gm to 4.0gm) before LL-37 instillation and before sacrifice. Inflammation and fibrosis were evaluated using tissue myeloperoxidase (MPO) concentration, collagen content, gross inspection, and microscopic histologic examination. RESULTS: SAGE GM-0111 reduced pain in treated animals significantly (54 ± 32% response rate) in animals exposed to LL-37 insult (96 ± 7% response rate, p<0.001) at 1g of stimulation. Collagen content, gross anatomy, histology with H&E and Masson’s trichrome staining indicated that fibrosis did not occur over the duration of the study. At the time of sacrifice there was no significant variation in tissue inflammation between groups. CONCLUSIONS: LL-37-induced cystitis yielded pain to be independent of inflammation. These findings further substantiate the physiological applicability of the LL-37-induced cystitis model to mimic human IC/PBS pathophysiology. Finally, our SAGE compound demonstrated potent non-opioid analgesic effects within this surrogate model. Source of Funding: NIH NIDDK R01 DK100868 (SO), Primary Children’s Hospital Integrated Science Award (SO), NIH K12 UL1RR025764 (SO), National Science Foundation Graduate Research Fellowship 1256065 (MMJ) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e97-e97 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Austin Schults* More articles by this author Wanjian Jia More articles by this author M. Martin Jensen More articles by this author Glenn Prestwich More articles by this author Siam Oottamasathien More articles by this author Expand All Advertisement PDF downloadLoading ...