Chronic pelvic pain is a poorly understood but sufficiently debilitating clinical condition primarily affecting women. Few diagnostic and treatment options are available for this understudied patient population, which is estimated at 9.2 million in the United States. The causes of chronic pelvic pain are numerous but may involve gynecologic, urologic, gastrointestinal, musculoskeletal, neuronal, or psychological origins as well as combinations thereof. The urinary bladder and colorecmm are two of the larger pelvic organs thought to be affected primarily in these disorders, and thus, it is not surprising that interstitial cystitis (IC) and irritable bowel syndrome (IBS) are two of the commonest causes of chronic pelvic pain. The observed overlap of chronic pelvic pain disorders such as IC and IBS suggests a common underlying etiology or even cross-organ (neurogenic) sensitization. Using a newly developed rodent model for studying afferent-mediated interactions of the pelvic organs in the rat, we will investigate the hypothesis that chronic irritation of the distal colon may adversely influence and sensitize urinary bladder afferents leading to neurogenic cystitis and its associated physiologic sequelae. The studies proposed in this application will attempt to shed more light on the overlap and etiology of chronic pelvic pain syndromes and the role of cross-organ, afferent sensitization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066658-02
Application #
6803568
Study Section
Special Emphasis Panel (ZRG1-UROL (51))
Program Officer
Mullins, Christopher V
Project Start
2003-09-30
Project End
2008-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
2
Fiscal Year
2004
Total Cost
$313,184
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Ustinova, Elena E; Fraser, Matthew O; Pezzone, Michael A (2010) Cross-talk and sensitization of bladder afferent nerves. Neurourol Urodyn 29:77-81
Liang, Ruomei; Ustinova, Elena E; Patnam, Radhika et al. (2007) Enhanced expression of mast cell growth factor and mast cell activation in the bladder following the resolution of trinitrobenzenesulfonic acid (TNBS) colitis in female rats. Neurourol Urodyn 26:887-93
Christianson, Julie A; Liang, Ruomei; Ustinova, Elena E et al. (2007) Convergence of bladder and colon sensory innervation occurs at the primary afferent level. Pain 128:235-43
Ustinova, Elena E; Gutkin, Dmitriy W; Pezzone, Michael A (2007) Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. Am J Physiol Renal Physiol 292:F123-30
Ustinova, Elena E; Fraser, Matthew O; Pezzone, Michael A (2006) Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. Am J Physiol Renal Physiol 290:F1478-87
Pezzone, Michael A; Liang, Ruomei; Fraser, Matthew O (2005) A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology 128:1953-64