Objective To determine whether oral cimetidine. which reportedly improves s
ymptoms in 60-70% of patients with painful bladder syndrome/interstitial cy
stitis 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 H-2 receptors and a proton pump.
Patients and methods Fourteen patients (13 women and one man, mean age 51 y
ears) with refractory bladder pain and irritative urinary symptoms were tre
ated 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 gas
trin, with counterstaining using toluidine blue, to detect mast cell granul
es containing histamine. Biopsies from normal areas of the bladder from an
age-matched control group of patients with transitional cell carcinoma of t
he bladder were stained similarly. Human stomach and colon were used as pos
itive controls for gastrin and toluidine blue, respectively. The clinical r
esponse to cimetidine was compared with the histology in a blinded fashion.
Results Eight of the patients responded well to cimetidine: none of the bio
psies 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 non-specific urothelial staining. Numerou
s mast cells with crimson granules and pale nuclei were visible in three pa
tients and fewer in three others: their presence or absence did not correla
te with the symptomatic response.
Conclusions Cimetidine is a useful medical treatment for bladder pain but t
he presence or absence of gastrin or histamine-like immunoreactivity does n
ot explain its therapeutic benefit.