Increased expression of growth-associated protein (GAP-43) in lower urinary tract pathways following cyclophosphamide (CYP)-induced cystitis.
Alterations in the expression of growth-associated protein 43 (GAP-43) were examined in lower urinary tract micturition reflex pathways in a chronic model of cyclophosphamide (CYP)-induced cystitis. In control animals, expression of GAP-43 was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the dorsal horn and (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1) and (4) in the lateral collateral pathway of Lissauer in L6-S1 spinal segments. Densitometry analysis has demonstrated significant increases (p</=0.001; 1.5-4.0-fold increase) in GAP-43-immunoreactivity (IR) in these regions of the rostral lumbar (L1-L2) and caudal lumbosacral (L6-S1) spinal cord following CYP-induced urinary bladder inflammation. Changes in GAP-43-IR were restricted to those segmental levels examined (L1-L2 and L6-S1) that are involved in lower urinary tract reflexes. Changes in GAP-43-IR were not observed at the L5 segmental level. In contrast to significant increases in GAP-43-IR in specific regions of the rostral lumbar and caudal lumbosacral spinal cord, no changes in GAP-43-IR were observed in the L1, L2 or L6, S1 dorsal root ganglia (DRG). In control animals, virtually all retrogradely labeled (Fast Blue) bladder afferent cells in the L1, L2 and L6, S1 DRG expressed GAP-43-IR. This percentage (approximately 100%) of bladder afferent cells expressing GAP-43-IR was unchanged following CYP-induced urinary bladder inflammation. Alterations in GAP-43-IR following chronic cystitis may suggest a reorganization of bladder afferent projections and spinal elements involved in bladder reflexes consistent with alterations in bladder function observed in animal models of cystitis.