Caffeine Ingestion Causes Detrusor Overactivity and Afferent Nerve Excitation in Mice

Abstract

We examined the effect of caffeine (Sigma®) on voiding patterns in mice and characterized potential changes in bladder function and sensory signaling. 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. 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. Oral caffeine administration results in detrusor overactivity and increased bladder sensory signaling in the mouse.