Pain is poorly managed in chronic pelvic pain, so new analgesic strategies are urgently needed. Our long-term goal is to harness the potential of probiotics to develop new probiotic analgesics for treating the pelvic pain of interstitial cystitis/bladder pain syndrome (IC). We previously examined the molecular basis that discriminates the symptomatic response to uropathogenic E. coli (UPEC) from the lack of response to E. coli clinically associated with asymptomatic bacteriuria (ASB). We have now accumulated compelling preliminary data demonstrating that E. coli-based probiotics alleviate both acute and chronic pelvic pain in clinically-relevant murine models that recapitulate key aspects of IC. Here, we hypothesize that specific LPS structures mediate ASB E. coli LPS analgesic activity that modulates downstream neuronal responses. These mechanistic studies will define the analgesic ligands of probiotic E. coli and demonstrate modulation of bladder afferent activity. These studies are highly innovative, and we are unaware of other groups studying analgesic probiotics for chronic pelvic pain. This project will thus result in a new mechanistic understanding of probiotic analgesics and provide critical pre-clinical data to drive these probiotics into clinical trials for IC.
|Effective start/end date||9/9/14 → 8/31/16|
- National Institute of Diabetes and Digestive and Kidney Diseases (1R56DK102807-01)