Neonatal bladder inflammation alters activity of adult rat spinal visceral nociceptive neurons

Purpose: This investigation examined the effect of inflammation produced by intravesical zymosan during the neonatal period on spinal dorsal horn neuronal responses to urinary bladder distension (UBD) as adults. Methods: Female rat pups (P14-P16) were treated with intravesical zymosan or with anesthesia-only. These groups of rats were subdivided forming four groups: half received intravesical zymosan as adults and half received anesthesia-only. One day later, rats were anesthetized, the spinal cord was transected at a cervical level and extracellular single-unit recordings of L6-S1 dorsal horn neurons were obtained. Neurons were classified as Type I-inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II - not inhibited by HNCS - and were characterized for Spontaneous Activity and responses to graded UBD (20-60 mm Hg). Results: 227 spinal dorsal horn neurons excited by UBD were characterized. In rats treated as neonates with anesthesia-only, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following adult intravesical zymosan treatment whereas Type I neurons demonstrated decreased spontaneous and UBD-evoked activity relative to controls. In rats treated as neonates with intravesical zymosan, the spontaneous and UBD-evoked activity of both Type I and Type II neurons increased following adult intravesical zymosan treatment relative to controls. Conclusions: Neonatal bladder inflammation alters subsequent effects of acute bladder inflammation on spinal dorsal horn neurons excited by UBD such that overall there is greater sensory neuron activation. This may explain the visceral hypersensitivity noted in this model system and suggest that impaired inhibitory systems may be responsible.