PD9-04 RECEPTOR CASCADE MEDIATING POST-UTI CHRONIC PAIN

Abstract

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2014PD9-04 RECEPTOR CASCADE MEDIATING POST-UTI CHRONIC PAIN John Rosen and David Klumpp John RosenJohn Rosen More articles by this author and David KlumppDavid Klumpp More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.786AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES E. coli evoke a spectrum of pain responses when instilled into the bladder, ranging from no pelvic pain to post-UTI chronic pain that persists after transient infection. Previous studies indicate that E. coli-induced pain is mediated by TLR4 independent of inflammation. Here, we evaluated the hypothesis that TRPV1 and/or CCR2 mediators of post-UTI chronic pain downstream of TLR4. METHODS Post-UTI chronic pain was evaluated in mice by tactile allodynia in response to von Frey filaments applied to the pelvic region. Viscero-motor reflex (VMR) of abdominal muscles in response to bladder distension with saline was used as an independent measure of visceral pain. Anxiety-like/depression-like behavior was quantified as a central manifestation of chronic pain using novelty-suppressed feeding (NSF). RESULTS Mice infected with E. coli strain S[phi]874 acquired chronic pelvic allodynia that persisted long after bacterial clearance. Treatment with the TRPV1 antagonist capsazepine at the time of infection signficantly inhibited the development of chronic allodynia. In contrast, capsazepine administered after the onset of chronic allodynia had no effect, and these allodynia findings were corroborated at the levels of VMR activity and NSF. Similarly, allodynia and VMR activity did not develop in TRPV1-deficient mice infected with S[phi]874. Induction of MCP-1 and CCR2 was noted in sacral DRGs, and administration of a CCR2 antagonist significantly reduced allodynia. CONCLUSIONS These data suggest that TRPV1 mediates the establishment of chronic pelvic pain in response to a transient E. coli infection but is not required for pain maintenance. Conversely, CCR2 is required for maintenance of post-UTI chronic pain. Together with previous studies, our data suggest that E. coli may induce chronic pelvic pain through a cascade of TLR4-TRPV1-CCR2 in the periphery. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e212-e213 Advertisement Copyright & Permissions© 2014MetricsAuthor Information John Rosen More articles by this author David Klumpp More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...