Latent bladder hypersensitivity induced by neonatal cystitis in rats unmasked by segmental but not hetero-segmental inflammation

Rats which experienced neonatal bladder inflammation (NBI) have been demonstrated to exhibit latent bladder hypersensitivity with a nociceptive component that becomes unmasked by a second inflammatory insult as an adult. Manifested as augmented reflex and neuronal responses to urinary bladder distension (UBD), these NBI-induced changes are revealed by using inflammation of nearby structures as an adult pretreatment. The effect of inflammation in distant structures is not known. These studies examined visceromotor reflex responses and lumbosacral spinal dorsal horn neuronal responses to UBD in rats and compared effects of segmental (hindpaw) versus hetero-segmental (forepaw or face) inflammatory pretreatments in 192 female Sprague-Dawley rats raised from birth. On postnatal days 14–16 these rats underwent either NBI or control procedures. As adults, these rats received control injections or 0.1 ml Complete Freund’s Adjuvant (CFA) injections into one of four sites. Three days later they were studied in reflex or spinal single-cell neuronal experiments where responses were evoked by UBD. Visceromotor responses to UBD were more robust in rats which had injections in the hindpaw (either side) but were not significantly affected by forepaw or facial injections. Similar results were identified in L6/S1 neurons with more robust UBD-evoked responses observed in rats receiving hindpaw CFA injections but not forepaw injections. These results indicate that latent bladder hypersensitivity induced by NBI is made manifest by segmental, but not hetero-segmental inflammatory stimuli. This observation correlates with pain in patients with interstitial cystitis who often have flares in symptoms associated with inflammation of nearby structures.