The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP(-/-) mice was (p < or = 0.01) greater in L1, L2, L5-S1 DRG compared to WT mice. CYP treatment in WT mice increased (p < or = 0.05) p-CREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP(-/-) mice (p < or = 0.01) increased (p < or = 0.01) p-CREB-IR in L6-S1 DRG compared to WT with CYP. In WT mice, bladder afferent cells (20-38%) in DRG expressed p-CREB-IR under basal conditions. With CYP, p-CREB-IR increased in bladder afferent cells (60-65%; L6-S1 DRG) in WT mice. In VIP(-/-) mice, bladder afferent cells (12-58%) expressed p-CREB-IR under basal conditions, and CYP increased p-CREB expression (78-84%) in L6-S1 DRG. Urinary bladder NGF expression in VIP(-/-) mice under basal conditions or after cystitis was significantly greater than WT. Detrusor smooth muscle thickness was significantly increased in VIP(-/-) mice. Bladder NGF expression may contribute to differences in p-CREB expression.