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Interstitial cystitis is a chronic syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The aggravation of interstitial cystitis symptoms by stress suggests involvement of the sympathetic nervous system. Studies have identified increased sympathetic nervous system activity in patients with interstitial cystitis but to our knowledge effects on bladder function have not been reported. To address this question we measured bladder norepinephrine (NE) content, the electrical field stimulation flux of NE and acetylcholine (ACh), and the effects of feline interstitial cystitis on adrenoceptor (AR) mediated bladder strip contractility.Bladders were obtained from healthy cats and cats with feline interstitial cystitis. In experiment 1 bladder tissue NE content was determined and the simultaneous release of 3H-NE and 14C-ACh in perfusion bath effluent after electrical field stimulation was measured. NE and ACh release was calculated from the area under the efflux curve. In experiment 2 electrical field stimulation induced contractility of bladder body strips was measured in the presence of 100 nM. to 25 microM. NE only or combined with atipamezole (an alpha2-AR antagonist), propranolol (a beta-AR antagonist) or phentolamine (an alpha-AR antagonist). Antagonists were added to the bath at least 15 minutes before stimulation, after which NE was added in cumulative doses and dose response curves were constructed.Significant increases in NE content and efflux in the absence of alterations in ACh efflux were identified. In the bladder strip studies decreased alpha2 and beta1-AR function was found in strips from cats with feline interstitial cystitis, whereas beta3 or atypical beta-ARs were tentatively identified.These results support and extend previous studies by identifying an effect of increased sympathetic activity on bladder function in cats with feline interstitial cystitis.

We systematically identified and evaluated various animal models that have been studied to help identify the underlying mechanisms of and possible treatment options for interstitial cystitis.Models of interstitial cystitis published between 1983 and 2001 were obtained by searching MEDLINE and other Internet databases using cystitis and model as the primary key words. Models with characteristics of interstitial cystitis similar to those defined by National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases criteria were reviewed. Some articles describing animal models with similar pathological conditions in other organs were also included to enlarge the base of potentially relevant material.We identified and evaluated some 16 animal models of interstitial cystitis, which we categorized as bladder inflammation induced by intravesical administration of an irritant or immune stimulant, systemic and environmentally induced inflammation, and a naturally occurring model of interstitial cystitis that occurs in cats. Some abnormalities identified in humans and cats with interstitial cystitis can be reproduced in healthy animals using luminal, systemic or environmental stimuli. At the level of the bladder the source of stimulation cannot be discriminated. Variability in the extent of bladder distention complicated the interpretation of some studies. In addition, the noxious stimuli used can affect many epithelial surfaces as well as the urothelium, suggesting they are nonspecific responses to injury rather than specific to interstitial cystitis.No model in bladder injury in healthy animals currently reproduces as many features of interstitial cystitis as the naturally occurring disease in cats. While induced models of relative injury may help to provide insight into the bladder response to injury, feline interstitial cystitis follows a similar chronic waxing and waning time course as does interstitial cystitis in humans, which may be more suitable for studying the effects of stressors on the severity of clinical signs as well as newly proposed therapies.