Cystitis-induced upregulation of tyrosine kinase (TrkA, TrkB) receptor expression and phosphorylation in rat micturition pathways.

This study examined tyrosine kinase receptor (Trk) expression and phosphorylation in lumbosacral dorsal root ganglia (DRG) after acute (8 or 48 hours) or chronic (10 days) cyclophosphamide (CYP)-induced cystitis. Increases in the number of TrkA-immunoreactive (IR) cell profiles were detected in the L1 and L6 DRG (four-fold; P < or = 0.01) and the S1 DRG (1.5-fold; P < or = 0.05) but not in the L2, L4, and L5 DRG with CYP-induced cystitis of acute and chronic duration compared with control rats. The number of TrkB-IR cell profiles increased in the L1 and L2 DRG (L1: 2.6-fold; L2: 1.4-fold; P < or = 0.05) and in the L6 and S1 DRG (L6: 2.2-fold; S1: 1.3-fold; P < or = 0.05) only after acute CYP treatment (8 hours). After CYP treatment, the percentage of bladder afferent cell profiles expressing TrkA-IR (approximately 50%; P < or = 0.05) increased in L1 and L6 DRG. The percentage of bladder afferent cell profiles expressing TrkB-IR (approximately 45%; P < or = 0.05) in L1, L2, L6, and S1 DRG also increased compared with control cell profiles. The increase in TrkA-IR in bladder afferent cells occurred 8 hours after CYP treatment and was maintained in L1 DRG with chronic (10 days) CYP-induced cystitis. However, the increase in bladder afferent cells expressing TrkB-IR only occurred at the most acute time point examined (8 hours). TrkA-IR and TrkB-IR cell profiles also demonstrated phosphorylated Trk-IR with acute and/or chronic CYP-induced cystitis. These results demonstrated that CYP-induced cystitis increases the expression and phosphorylation of Trk receptors in lumbosacral DRG. Expression of neurotrophic factors in the inflamed urinary bladder may contribute to this increased expression, and neurotrophic factor and Trk interactions may play unique roles in decreased urinary tract plasticity with CYP-induced cystitis. Copyright 2002 Wiley-Liss, Inc.