OBJECTIVE: To study the role of transient receptor potential melastatin 2 in bladder function and inflammation-associated hypersensitivity. METHODS: We evaluated physiological function of the bladder and intravesical lipopolysaccharide-induced inflammatory nociceptive responses in female wild-type and transient receptor potential melastatin 2-knockout mice. In vivo frequency/volume and decerebrated unanesthetized cystometry measurements, as well as in vitro detrusor strip functional studies, were carried out to evaluate bladder function. Mice received intravesical lipopolysaccharide (2.0 mg/mL) or saline instillation to evaluate responses to bladder inflammation. Voiding and bladder pain-like behaviors, cystometry measurements and histological evaluation were carried out before and after intravesical lipopolysaccharide instillation. RESULTS: Few phenotypic differences in in vivo and in vitro physiological function were found between the two genotypes. Comparison of measurements taken before and 24-48 h after intravesical lipopolysaccharide instillation showed that voiding parameters did not change in transient receptor potential melastatin 2-knockout mice, whereas an increased voiding frequency was observed in wild-type mice. At 24 h after intravesical lipopolysaccharide instillation, the numbers of bladder pain-like behaviors and of infiltrated inflammatory cells in the bladder submucosal layer were significantly increased, and the voided volume and the intercontraction interval were significantly decreased on cystometry measurements in wild-type mice compared with those in both transient receptor potential melastatin 2-knockout mice and in wild-type mice treated with saline instillation. CONCLUSIONS: Although the physiological roles of transient receptor potential melastatin 2 channels in the bladder might be limited, inflammation and associated hypersensitivity of the bladder caused by intravesical lipopolysaccharide instillation are attenuated in transient receptor potential melastatin 2-knockout mice, suggesting pathophysiological roles of transient receptor potential melastatin 2 channels in these processes.