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Am J Physiol Renal Physiol 297: F1038-F1044, 2009. First published July 22, 2009; doi:10.1152/ajprenal.00110.2009
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Involvement of JAK-STAT signaling/function after cyclophosphamide-induced bladder inflammation in female rats

Bopaiah P. Cheppudira,1 Beatrice M. Girard,2 Susan E. Malley,1 Abbey Dattilio,1 Kristin C. Schutz,2 Victor May,2 and Margaret A. Vizzard1,2

Departments of 1 Neurology and ; 2Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont

Submitted February 25, 2009 ; accepted in final form July 20, 2009

Cytokines are upregulated in a variety of inflammatory conditions and cytokine/receptor interactions can activate JAK-STAT signaling. Previous studies demonstrated upregulation of numerous cytokines in the urinary bladder following cyclophosphamide (CYP)-induced cystitis. The role of JAK-STAT signaling in urinary bladder inflammation and referred somatic sensitivity has not been addressed. The contribution of JAK-STAT signaling pathways in CYP-induced bladder hyperreflexia and referred somatic hypersensitivity was determined in CYP-treated rats using a JAK2 inhibitor, AG490. Acute (4 h; 150 mg/kg ip), intermediate (48 h; 150 mg/kg ip), or chronic (75 mg/kg ip, once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Phosphorylation status of STAT-3 was increased in urinary bladder after CYP-induced cystitis (4 h, 48 h, chronic). Blockade of JAK2 with AG490 (5–15 mg/kg ip or intravesical) significantly (P ≤ 0.05) reduced bladder hyperreflexia and hind paw sensitivity in CYP-treated rats. These studies demonstrate a potential role for JAK-STAT signaling pathways in bladder hyperreflexia and referred pain induced by CYP-induced bladder inflammation.

somatic sensitivity; bladder hyperreflexia; cystometry; AG490


Address for reprint requests and other correspondence: M. A. Vizzard, Dept. of Neurology, Univ. of Vermont College of Medicine, D415A Given Research Bldg., Burlington, VT 05405 (e-mail: margaret.vizzard{at}uvm.edu).






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