Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 322, Issue 1, Pages F1-F13Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00167.2021
Keywords
bladder afferents; pain; sensory neurons; urinary bladder; urinary tract infection
Categories
Funding
- Urology Care Foundation Research Scholar Award Program
- National Institute of Diabetes and Digestive and Kidney Diseases [R01DK119183]
- Physiology and Model Systems Core of the Pittsburgh Center for Kidney Research Grant [P30DK079307]
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This study suggests that bacterial infection can cause sensitization of bladder sensory neurons, leading to bladder overactivity and pelvic pain.
Urinary tract infections (UTIs) cause bladder hyperactivity and pelvic pain, but the underlying causes of these symptoms remain unknown. We investigated whether afferent sensitization contributes to the bladder overactivity and pain observed in mice suf-fering from experimentally induced bacterial cystitis. Inoculation of mouse bladders with the uropathogenic Escherichia coli strain UTI89 caused pelvic allodynia, increased voiding frequency, and prompted an acute inflammatory process marked by leukocytic infiltration and edema of the mucosa. Compared with controls, isolated bladder sensory neurons from UTI-treated mice exhibited a depolarized resting membrane potential, lower action potential threshold and rheobase, and increased firing in response to suprathreshold stimulation. To determine whether bacterial virulence factors can contribute to the sensitization of bladder affer-ents, neurons isolated from naive mice were incubated with supernatants collected from bacterial cultures with or depleted of li-popolysaccharide (LPS). Supernatants containing LPS prompted the sensitization of bladder sensory neurons with both tetrodotoxin (TTX)-resistant and TTX-sensitive action potentials. However, bladder sensory neurons with TTX-sensitive action potentials were not affected by bacterial supernatants depleted of LPS. Unexpectedly, ultrapure LPS increased the excitability only of bladder sensory neurons with TTX-resistant action potentials, but the supplementation of supernatants depleted of LPS with ultrapure LPS resulted in the sensitization of both population of bladder sensory neurons. In summary, the results of our study indicate that multiple virulence factors released from UTI89 act on bladder sensory neurons to prompt their sensitization. These sensitized bladder sensory neurons mediate, at least in part, the bladder hyperactivity and pelvic pain seen in mice inocu-lated with UTI89. NEW & NOTEWORTHY Urinary tract infection (UTI) produced by uropathogenic Escherichia coli (UPEC) promotes sensitization of bladder afferent sensory neurons with tetrodotoxin-resistant and tetrodotoxin-sensitive action potentials. Lipopolysaccharide and other virulence factors produced by UPEC contribute to the sensitization of bladder afferents in UTI. In conclusion, sensi-tized afferents contribute to the voiding symptoms and pelvic pain present in mice bladder inoculated with UPEC.
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