Enhanced mucosal contractile activity following rapid, reversible inhibition of bladder activity by dimethyl sulfoxide (DMSO)

Abstract Purpose Intravesical dimethyl sulfoxide (DMSO) is used to treat interstitial cystitis/bladder pain syndrome, but its mechanisms of action are not fully understood. The study aim was to investigate the effects of DMSO on contractility of the bladder detrusor and the mucosa (urothelium/lamina propria). Methods Contractile responses of isolated detrusor muscle from pig and human bladder were observed in the absence and presence of DMSO (1.7–25%), and after 4 h of washing. The effects of DMSO and recovery were also examined in strips of pig bladder mucosa (urothelium/lamina propria). Results In detrusor strips from pig and human, DMSO inhibited contractions to carbachol and at the highest concentration (25%) responses were completely abolished in all tissues. However, after a 4-hour washing period, detrusor responses to carbachol recovered completely. Isolated mucosal strips spontaneously developed phasic contractile activity that was completely abolished within 10 min of DMSO (25%) exposure. Basal tension was also reduced by 49.1 ± 9.4%. The effects of DMSO on the mucosa were rapidly reversed with washing. Contractile activity was completely recovered to initial levels within 12.6 ± 2.9 min and was enhanced above initial levels by 24 ± 2 min. Responses to carbachol, isoprenaline and neurogenic responses were completely abolished by DMSO (25%), but responses recovered completely following washing and carbachol responses significantly enhanced. Conclusion These results demonstrate the powerful, but reversible, effects of DMSO on detrusor and mucosal contractile activity. The enhanced mucosal contractile activity upon washout may explain the flare up of symptoms observed in some patients following treatment.