Purpose: Painful bladder disorders vary in intensity with the menstrual cycle in women. We evaluated the influence of the correlate in rats (the estrous cycle) on the nociceptive visceromotor reflex to bladder distention in the presence/absence of inflammation and of spinal opioid blockade. Materials and Methods: We recorded visceromotor reflexes as electromyogram responses of the abdominal musculature to graded (10 to 60 mm Hg) bladder distention in anesthetized female rats in the presence of intrathecal saline or naloxone (10 μg) 1 day after receiving intravesical zymosan or anesthesia alone. Results: In saline treated rats visceromotor reflexes to bladder distention were significantly greater in those with an inflamed vs a noninflamed bladder when examined together. When separated into phases, rats with bladder inflammation showed complex estrous cycle effects with significantly greater visceromotor reflexes to bladder distention during metestrus and proestrus than diestrus. In naloxone treated rats visceromotor reflexes to bladder distention were significantly greater in those with an inflamed vs a noninflamed bladder when examined together. Naloxone enhanced the overall magnitude of visceromotor reflexes to bladder distention in the inflamed and noninflamed conditions. The magnitude of visceromotor reflexes to bladder distention in noninflamed and inflamed conditions in the presence of naloxone was estrous phase dependent in the order, estrus >metestrus >diestrus >proestrus. Similar findings were apparent on analysis of data on responses at threshold intensity (30 mm Hg). Conclusions: Data suggest that circulating hormones present during the estrous cycle alter bladder reactivity and opioid modulatory systems to maintain constancy of input from the bladder to the central nervous system. © 2010 American Urological Association Education and Research, Inc.