Interstitial cystitis/painful bladder syndrome (IC/PBS) is a clinical situation characterized with chronic bladder or pelvic pain, which is often accompanied with frequency and urgency. The exact etiology of IC/PBS remains unclear, while several studies suggest associations between IC/PBS with aberrant mast cell behavior. Doxylamine is a first-generation histamine receptor H1 antagonist with anticholinergic function. Doxylamine has demonstrated safety in prior studies, and reported studies clue its potential efficacy of IC/PBS. This study aims to evaluate the potential efficacy of doxylamine in alleviating IC/PBS and to elucidate the underlying mechanisms.

A cyclophosphamide (CYP)-induced cystitis mouse model was employed in this study. Experimental groups received oral doxylamine via gavage. Control groups were administered equal volume of vehicle. After intervention, allodynia and voiding behaviors were monitored. Bladder inflammatory markers and histopathological features were further analyzed.
In this study, mouse cystitis  models were induced  via intraperitoneal CYP injection. Doxylamine or vehicle was administered orally . Mechanical hyperalgesia in lower abdominal region overlying the bladder was detacted via von Frey filaments. Voiding frequency and volume was quantified with voiding-spot assay. Bladders were harvested for histological analysis (H&E staining) and mast cell degranulation assay (toluidine blue staining). Inflammatory cytokines (IL-6, IL-1β，TNF-α,) were measured via ELISA.

Doxylamine-treated mice behaved significantly reduced mechanical hyperalgesia compared to control mice. Voiding frequency was also decreased among doxylamine-treated mice  Histologically, doxylamine attenuated CYP-induced bladder edema and inflammatory infiltration. Mast cell degranulation was markedly suppressed accompanied with decreased IL-6, IL-1β and TNF-α levels.

Doxylamine ameliates mechanical hyperalgesia and voiding dysfunction (frequency) in CYP-induced mice. The results may correlate with inhibition of mast cell degranulation and pro-inflammatory cytokines release.  However, the anticholinergic efficacy of doxylamine among this remains to reveal.

Doxylamine demonstrates significant efficacy in alleviating CYP-induced symptoms in mice, potentially through mast cell stabilization and anti-inflammatory mechanisms. These findings support its translational potential as a novel therapeutic choice for IC/PBS.