Cimetidine in painful bladder syndrome: a histopathological study

To determine whether oral cimetidine, which reportedly improves symptoms in 60-70% of patients with painful bladder syndrome/interstitial cystitis has a similar mechanism of action on the human bladder and involving a similar peptidergic pathway as it has in human stomach, where it alters histamine-gastrin reactions mediated via H2 receptors and a proton pump.

Fourteen patients (13 women and one man, mean age 51 years) with refractory bladder pain and irritative urinary symptoms were treated with cimetidine. The response to cimetidine was assessed by outpatient follow-up and an analogue pain score. Bladder biopsies from eight patients were stained with haematoxylin and eosin, and a polyclonal antibody to gastrin, with counterstaining using toluidine blue, to detect mast cell granules containing histamine. Biopsies from normal areas of the bladder from an age-matched control group of patients with transitional cell carcinoma of the bladder were stained similarly. Human stomach and colon were used as positive controls for gastrin and toluidine blue, respectively. The clinical response to cimetidine was compared with the histology in a blinded fashion.

Eight of the patients responded well to cimetidine; none of the biopsies showed evidence of carcinoma in situ. Although G cells in the stomach stained well for gastrin none of the bladder biopsies showed gastrin-like immunoreactivity, apart from some nonspecific urothelial staining. Numerous mast cells with crimson granules and pale nuclei were visible in three patients and fewer in three others; their presence or absence did not correlate with the symptomatic response.

Cimetidine is a useful medical treatment for bladder pain but the presence or absence of gastrin or histamine-like immunoreactivity does not explain its therapeutic benefit.