Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis – significance in the responsiveness to antihistamine treatment and disease symptoms

Abstract

BackgroundActivation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms.MethodsBladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed.ResultsThe expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found.ConclusionThe present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).

Clinical Observation of the Correlation Between Overactive Bladder and Atopic Constitution in Children

“…Meanwhile, mast cells can be visible in the uroepithelial, lamina propria, and smooth muscle layers of the bladder wall. The activation of mast cells causes the release of histamine, the binding of which to the receptors on the bladder wall causes inflammation and bladder sensitization (20). Moreover, histamine can also increase the afferent nerve's bladder sensitivity via H1 receptors, leading to overactive bladder contractions (21).…”

Does cystoscopy method affect the investigation of bladder pain syndrome/interstitial cystitis?

“…Release of histamine from MCs is considered to be related to inflammation and hypersensitivity of the bladder. Shan et al studied the expression of histamine receptors within the bladder of women with BPS/IC [ 30 ] and identified increased expression of all four histamine receptors in the BPS/IC group compared with the control group. Although we report no treatment outcomes for this study, the authors would explore the association of bladder mastocytosis with a possible diagnosis of MC activation syndrome and would consider treatment with a trial of diet restrictions to avoid MC-liberating foods in combination with MC-stabilising or suppression therapy [ 31 , 32 ].…”

Phenotypes of BPS/IC

“…However, data regarding mast cells is mixed with a recent study showing higher levels of mast cells in non-Hunner's lesion patients [71]. Interestingly, a recent study has shown that histamine receptor expression is upregulated in patients with BPS/IC, but this did not predict response to antihistamine treatment [72]. The question of whether an elevated mast cell count represents a distinct phenotype of BPS independent of the presence of Hunner's lesions remains to be determined.…”

“…A small retrospective study compared the outcomes of amitriptyline treatment in patients with BPS/IC stratified according to ESSIC criteria and found no difference in efficacy between ESSIC type 1 and ESSIC type 3 patients [28]. Similarly, another retrospective study comparing antihistamine responders to non-responders found no correlation between the expression levels of histamine receptors and treatment outcome, although patients were not stratified by cystoscopic features [72]. Outcomes from intravesical hyaluronic acid instillations cannot be predicted by the presence or absence of Hunner's lesions, and data for superior efficacy for intravesical dimethylsulfoxide (DMSO) in Hunner's lesion patients compared with non-Hunner's lesion patients comes from a small, retrospective study [78,79].…”