Current analgesics are limited due to adverse side effects including addiction and organ damage. Indeed, the need for novel analgesics is highlighted as a High Priority by NCCAM. Our long-term goal is to harness the potential of probiotics to develop new probiotic analgesics for treating 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. We hypothesize that the analgesic activity of E. coli-based probiotics results from acting on three receptors involved in bladder pain signals, Toll- like receptor 4 (TLR4), transient receptor potential cation channel subfamily V member 1 (TRPV1), and chemokine C-C motif receptor 2 (CCR2). These mechanistic studies will define the analgesic ligands of probiotic E. coli and define the roles for each receptor in mediating pelvic pain in murine models of IC. 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.

Public Health Relevance

New analgesics are desperately needed due to adverse side effects. Probiotics are widely accepted by the public and offer an ideal platform for delivering analgesics safely and effectively. This innovative study will determine the mechanisms of novel analgesic probiotics of treating interstitial cystitis/painful bladder syndrome.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AT007701-01A1
Application #
8629275
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Duffy, Linda C
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Urology
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60611