Cimetidine in painful bladder syndrome: a histopathological study

Abstract

Objective 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 H 2 receptors and a proton pump. Patients and methods 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. Results 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 nonspeci®c 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. Conclusions 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 bene®t.

Mast Cell-Derived Histamine Mediates Cystitis Pain

“…The H2R antagonist cimetidine produced significant improvement in pain and nocturia in a limited trial of PBS patients [31]. Similar to our findings that PRV-induced pain mediated histamine is independent of TNF, symptom relief from cimetidine therapy was not associated with improved bladder pathology [39]. Pilot clinical studies yielded modest pain relief in IC patients receiving the old-line H1R antagonist hydroxyzine [40], but studies have not yet been conducted with newer generation H1R antagonists.…”

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

“…Two very small observational trials 81,82 and one placebocontrolled RCT 83 have shown an improvement in symptoms of IC/BPS with cimetidine at various dosages. Thilagarajah et al 83 randomized 36 patients to cimetidine 400 mg orally twice daily vs. placebo and reported a significant improvement in symptoms in the cimetidine vs. placebo groups, respectively.…”

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

“…Atropine-resistant, ATP-mediated detrusor contractions have been shown to increase with age [42]. Histamine can evoke calcium transients in cultured human detrusor smooth muscle cells [43], and histamine receptors have been the target of IC therapy with H1 [44] or H2 [45] selective antihistaminics. Therefore, we routinely analyze the expression of muscarinic (M2, M3), purinergic (P2X1, P2X2, P2X3), and histamine (H1, H2) receptors in the detrusor smooth muscle cells by confocal immunofluorescence.…”