title: Phosphorylation of extracellular signal-regulated kinases in bladder afferent pathways with cyclophosphamide-induced cystitis.
abstract: Extracellular signal-regulated kinases (ERK1 and ERK2) are phosphorylated in the nervous system after somatic or visceral stimulation or inflammation and play roles in central sensitization and pain hypersensitivity. ERK1/2 activation with cyclophosphamide (CYP)-induced cystitis has been demonstrated in urinary bladder and inhibitors of ERK1/2 phosphorylation reduce CYP-induced bladder hyperreflexia. In this study, we determined pERK1/2 expression and regulation in lumbosacral dorsal root ganglia (DRG) and spinal cord with CYP-induced cystitis (4 h, 48 h, chronic) using Western blotting and immunohistochemical techniques. Phosphorylated extracellular signal-regulated kinases (pERK1/2) expression was significantly (P< or =0.01) upregulated in L6 and S1 DRG with CYP-induced cystitis with the greatest upregulation occurring at 4 h. No changes in pERK1/2 expression were observed in L1, L2 or L5 DRG or in any spinal cord segment examined (L1, L2, L5-S1) with CYP-induced cystitis. Cytoplasmic pERK1/2-immunoreactivity (IR) and pericellular pERK1/2-IR was observed in all DRG examined from control rats and cytoplasmic pERK1/2-IR was significantly (P< or =0.01) increased in L6 and S1 DRG with 4 and 48 h CYP-induced cystitis. In contrast, pericellular pERK1/2-IR in DRG was not regulated by CYP-induced cystitis. A small percentage of bladder afferent cells in lumbosacral DRG expressed pERK1/2-IR in control rats; however, CYP-induced cystitis (48 h) significantly (P< or =0.01) increased the percentage of bladder afferent cells in the L6 and S1 DRG exhibiting pERK1/2-IR. These studies suggest that activation of the ERK pathway in lumbosacral DRG may play a role in neuroplasticity in micturition reflexes with CYP-induced cystitis.
authors.affiliation: Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Corrow
authors.forename: M A
authors.initials: MA
authors.lastname: Vizzard
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000633:toxicity; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation* / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3