The long-term goal of this research is to determine the role of the sensory and sympathetic limbs of the nervous system on the pathophysiology of interstitial cystitis (IC). IC is a painful, inflammatory bladder disease of human beings. The symptoms of IC (pain and increased urinary frequency and urgency) may be exacerbated by stressful experience. The cause(s) is (are) unknown. A significant impediment to progress in understanding IC has been the lack of an animal model of the disease. Using NIDDK grant DK 47537, the principal investigator has shown that the majority of cats presented to veterinarians for care of irritative voiding meet all of the objective criteria for diagnosis of IC in humans that can be applied to animals. Moreover, the natural history and pathophysiologic features are comparable in both species, making IC in cats an excellent spontaneously occurring disease model. This four year proposal is intended to use cats with IC to achieve the following objectives: 1) to determine if inhibiting sensory afferent neurons with capsaicin, or sympathetic efferent neurons with 6-hydroxydopamine, permits resolution of the clinical, bladder, and afferent, central and efferent nervous system abnormalities present in IC; 2) to determine the effects of IC and drug administration on in-vitro bladder strip contractility; and 3) to determine the long-term (6 month) effects of the drug that results in the greatest resolution of bladder abnormalities. The correlation of the clinical effects of these drugs with their effects on the bladder and nervous system should provide important new insights on the mechanisms underlying many of the abnormalities observed in patients with IC, and suggest more rational approaches to treatment of the disease than currently are available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047538-07
Application #
6380854
Study Section
Special Emphasis Panel (ZRG4-UROL (01))
Program Officer
Mullins, Christopher V
Project Start
1993-09-30
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2003-06-30
Support Year
7
Fiscal Year
2001
Total Cost
$183,601
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Buffington, C A T (2011) Idiopathic cystitis in domestic cats--beyond the lower urinary tract. J Vet Intern Med 25:784-96
Sculptoreanu, Adrian; de Groat, William C; Buffington, C A Tony et al. (2005) Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline interstitial cystitis. Exp Neurol 193:437-43
Sculptoreanu, Adrian; de Groat, William C; Buffington, Charles A et al. (2005) Protein kinase C contributes to abnormal capsaicin responses in DRG neurons from cats with feline interstitial cystitis. Neurosci Lett 381:42-6
Buffington, C A Tony (2004) Comorbidity of interstitial cystitis with other unexplained clinical conditions. J Urol 172:1242-8
March, Philip A; Muir 3rd, William W (2003) Use of the bispectral index as a monitor of anesthetic depth in cats anesthetized with isoflurane. Am J Vet Res 64:1534-41
Westropp, Jodi L; Welk, Kristin A; Buffington, C A Tony (2003) Small adrenal glands in cats with feline interstitial cystitis. J Urol 170:2494-7
Westropp, Jodi L; Buffington, C A Tony (2002) In vivo models of interstitial cystitis. J Urol 167:694-702
Buffington, C A Tony (2002) External and internal influences on disease risk in cats. J Am Vet Med Assoc 220:994-1002
Wheeler, Marcia A; Hausladen, Derek A; Yoon, Jeong H et al. (2002) Prostaglandin E2 production and cyclooxygenase-2 induction in human urinary tract infections and bladder cancer. J Urol 168:1568-73
Buffington, C A Tony; Teng, Bunyen; Somogyi, George T (2002) Norepinephrine content and adrenoceptor function in the bladder of cats with feline interstitial cystitis. J Urol 167:1876-80

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