Host responses to urinary tract infections and emerging therapeutics: Sensation and pain within the urinary tract

Lori A. Birder*, David J. Klumpp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Urinary tract infection (UTI) pathogenesis is understood increasingly at the level of the uropathogens and the cellular and molecular mediators of host inflammatory responses. However, little is known about the mediators of symptoms during UTI and what distinguishes symptomatic events from asymptomatic bacteriuria. Here, we review bladder physiology and sensory pathways in the context of an emerging literature from murine models dissecting the host and pathogen factors mediating pain responses during UTI. The bladder urothelium is considered a mediator of sensory responses and appears to play a role in UTI pain responses. Virulence factors of uropathogens induce urothelial damage that could trigger pain due to compromised bladder-barrier function. Instead, bacterial glycolipids are the major determinants of UTI pain independent of urothelial damage, and the O-antigen of lipopolysaccharide modulates pain responses. The extent of pain modulation by O-antigen can have profound effects, from abolishing pain responses to inducing chronic pain that results in central nervous system features reminiscent of neuropathic pain. Although these effects are largely dependent upon Toll-like receptors, pain is independent of inflammation. Surprisingly, some bacteria even possess analgesic properties, suggesting that bacteria exhibit a wide range of pain phenotypes in the bladder. In summary, UTI pain is a complex form of visceral pain that has significant potential to inform our understanding of bacterial pathogenesis and raises the specter of chronic pain resulting from transient infection, as well as novel approaches to treating pain.

Original languageEnglish (US)
Article numberUTI-0023-2016
JournalMicrobiology Spectrum
Issue number5
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Genetics
  • Immunology and Microbiology(all)
  • Physiology
  • Cell Biology
  • Ecology


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