Caffeine ingestion causes detrusor overactivity and afferent nerve excitation in mice

PURPOSE: We examined the effect of caffeine (Sigma®) on voiding patterns in mice and characterized potential changes in bladder function and sensory signaling.

MATERIALS AND METHODS: A total of 12 mice were fed high dose (150 mg/kg) caffeine daily for 2 weeks. Micturition frequency and volume were recorded at baseline and at the end point. The effects of chronic low dose (10 mg/kg) caffeine on voiding patterns were examined in 7 mice, which were subsequently studied using awake cystometry. In a separate study to characterize the effects of acute caffeine consumption on bladder function and sensory signaling cystometry was performed in 6 mice. Bladder extracellular multifiber afferent signaling was recorded at baseline and 1 hour after feeding low dose caffeine. In a separate group of mice baseline cystometrograms were done using normal saline, followed by a caffeine filling solution.

RESULTS: Compared to pretreatment conditions, daily oral high dose caffeine resulted in a significant increase in average micturition frequency and a decreased average volume per void. In animals fed low dose caffeine cystometry demonstrated a statistically significant increase in filling and threshold bladder pressure compared to caffeine naïve animals. Acute low dose caffeine ingestion resulted in a significant increase in filling pressure, an increased frequency of nonvoiding bladder contractions, a decrease in cystometric capacity and a 7.2-fold increase in the average firing rate of afferent nerves during filling. Caffeine administered intravesically had no effect on cystometric parameters.

CONCLUSIONS: Oral caffeine administration results in detrusor overactivity and increased bladder sensory signaling in the mouse.