related differences in lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of intercontraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than in female mice [19 Ϯ 5% (P ϭ 0.03) vs. 65 Ϯ 5% (P ϭ 0.03); n ϭ 6 for each], exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P ϭ 0.002). A/A reduced maximal voiding pressure (MVP) (19 Ϯ 4%, P ϭ 0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P ϭ 0.56) in females, whereas A/A did not change MVP (P ϭ 1.00) but increased PT (16 Ϯ 4%, P ϭ 0.03) in males. A/A decreased bladder compliances of female and male mice in a similar fashion (44 Ϯ 10% vs. 24 Ϯ 7%, P ϭ 0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrates the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome. afferent; bladder tonus; detrusor contractility; efferent; urethral resistance NUMEROUS IN VIVO PHYSIOLOGICAL and pharmacological studies examining bladder and urethral activity have been conducted exclusively in one sex of animals in each experimental design, and thus it is uncertain whether functional responses of female and male lower urinary tracts are similar. There are only a few articles detailing differences between females and males in the lower urinary tract functions. Of the available reports, for example, one previous study comparing female and male rats in cystometry revealed that volume thresholds for inducing micturition were changed in accordance with altered intravesical infusion rates in the female rat, whereas these were constant regardless of the bladder filling rates in the male (24). The study suggested the possibility that mechanosensory afferent responses to intensity of the mechanical stimulus were different between the female and male animals.Epidemiologic studies have demonstrated sex-specific differences in prevalence and incidence of certain diseases. In the urological field, it has been well documented that prevalence and incidence of interstitial cystitis, which is a syndrome consisting of severe refractory bladder symptoms such as suprapubic pain, urinary frequency, and urgency without a specific identifiable cause, for women are significantly higher than those for men (10). What pathophysiological factors are involved in these sex-related differences?Here, we proposed the possibilities that sex differences in mechanisms responsible for transmitting inflammatory pai...