Pharmacological validation of a model of cystitis pain in the mouse

Interstitial cystitis (IC) is a chronic pelvic-perineal pain syndrome of unknown etiology that mainly targets the lower urinary tract. Pain is the most prominent feature of IC and current therapies provide limited relief. Novel treatment options for IC could be identified if more predictive animal models were available. A rat model based on administration of cyclophosphamide (CP) mimics the symptoms of IC and has been well characterized. However, experiments in mice have not consistently reported both the spontaneous and evoked pain behaviors. The current series of studies demonstrate that CP (200-400mg, i.p.) increased both spontaneous and evoked pain behaviors in mice. Additionally, clinically relevant compounds: morphine (1-10mg/kg), ketorolac (1-5.6mg/kg) and duloxetine (3-30mg/kg) all significantly reversed pain behaviors. In contrast, gabapentin (56mg/kg) had no effect. Thus, CP-induced cystitis in mice may be used to evaluate novel therapeutics for the treatment of pain due to interstitial cystitis.