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The expression of phosphorylated cAMP response element binding protein (pCREB) in dorsal root ganglia (DRG) with and without CYP-induced cystitis (150 mg/kg, i.p; 48 hr) was determined in VIP −/− and wildtype (WT) mice. p-CREB-immunoreactivity (IR) was determined in bladder (Fastblue) afferent cells. Nerve growth factor (NGF) bladder content was determined by ELISAs. Basal expression of pCREB-IR in DRG of VIP −/− mice was (p ≤ 0.01) greater in L1, L2, L5-S1 DRG compared to WT mice. CYP treatment in WT mice increased (p ≤ 0.05) pCREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP −/− mice (p ≤ 0.01) increased (p ≤ 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 pCREB-IR under basal conditions. With CYP, pCREB-IR increased in bladder afferent cells (60-65%; L6-S1 DRG) in WT mice. In VIP −/− mice, bladder afferent cells (12-58%) expressed pCREB-IR under basal conditions and CYP increased pCREB 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 pCREB expression.