Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis

Abstract

These studies examined changes in the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in micturition reflex pathways after chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, PACAP immunoreactivity was expressed in fibers in the superficial dorsal horn at all segmental levels examined (L1, L2, and L4–S1). Bladder afferent cells (40–45%) in the dorsal root ganglia (DRG; L1, L2, L6, and S1) from control animals also exhibited PACAP immunoreactivity. After chronic, CYP-induced cystitis, PACAP immunoreactivity increased dramatically in spinal segments and DRG (L1, L2, L6, and S1) involved in micturition reflexes. The density of PACAP immunoreactivity was increased in the superficial laminae (I–II) of the L1, L2, L6, and S1 spinal segments. No changes in PACAP immunoreactivity were observed in the L4–L5 segments. Staining also increased dramatically in a fiber bundle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the dorsal horn to the sacral parasympathetic nucleus in the L6–S1 spinal segments (lateral collateral pathway of Lissauer). After chronic cystitis, PACAP immunoreactivity in cells in the L1, L2, L6, and S1 DRG increased significantly (P ≤ 0.0001), and the percentage of bladder afferent cells expressing PACAP immunoreactivity also increased significantly (P ≤ 0.0001; 70–85%). No changes were observed in the L3–L5 DRG. These studies suggest that the neuropeptide, PACAP, may play a role in urinary bladder afferent pathways after visceral (urinary bladder) inflammation. Changes in PACAP expression after cystitis may play a role in altered visceral sensation (allodynia) and/or urinary bladder hyperreflexia in the clinical syndrome, interstitial cystitis. J. Comp. Neurol. 420:335–348, 2000. © 2000 Wiley-Liss, Inc.