Our goal was to evaluate the pain response in an LL-37 induced murine model for interstitial cystitis/painful bladder syndrome (IC/PBS). In particular, we sought to characterize the dose dependence, time-course, and relationship of LL-37 induced bladder inflammation and pain. The IC/PBS model was induced in C57Bl/6 mice by instilling 50 μL of LL-37, an immunomodulatory human cathelicidin (anti-microbial peptide), in the bladder for 1 hr. Pain responses were measured using von Frey filaments (0.04 gm to 4.0 gm) before and after LL-37 instillation. Inflammation was evaluated using tissue myeloperoxidase (MPO) assay, gross inspection, and microscopic histologic examination. The dose response experiment demonstrated a graded pain response, with higher concentrations of LL-37 challenge yielding higher pain responses across all stimuli tested. Statistical significance was seen when comparing 1.0 gm von Frey filament results at 320 μM (68 ± 8% response) vs. 0 μM (38 ± 6% response). Interestingly, pain responses did not attenuate across time but increased significantly after 5 (p=0.0012) and 7 days (p=0.0096). Comparison with MPO data suggested that pain responses could be independent of inflammation. We demonstrated within our LL-37 induced IC/PBS model pain occurs in a dose-dependent fashion, pain responses persist beyond the initial point of insult, and our dose response and time course experiments demonstrated that pain was independent of inflammation.
American journal of clinical and experimental urology. 2017 Sep 01*** epublish ***
Wanjian Jia, Austin J Schults, Mark Martin Jensen, Xiangyang Ye, Jeremiah A Alt, Glenn D Prestwich, Siam Oottamasathien
Division of Urology, Section of Pediatric Urology, University of UtahSalt Lake City, UT., Department of Bioengineering, University of UtahSalt Lake City, UT., Department of Pharmacotherapy, University of UtahSalt Lake City, UT., Center for Therapeutic Biomaterials, Department of Medicinal Chemistry, University of UtahSalt Lake City, UT.