DMSO - EFFECT ON BLADDER AFFERENT NEURONS AND NITRIC-OXIDE RELEASE

Purpose: Interstitial cystitis (IC), a chronic disorder of the urinary bladder, is characterized by increased voiding frequency, urgency and pain. Patients with IC also exhibit reduced urinary nitric oxide synt hase activity. Intravesical administration of dimethyl sulfoxide (DMSO ) has been used to provide symptomatic relief in patients with IC. The present experiments were undertaken to determine if intravesical DMSO affects neural pathways involved in bladder function in the rat and i f DMSO can influence the release of nitric oxide in the bladder or fro m afferent neurons. Materials and Methods: The effects of intravesical DMSO (10% solution in saline) on reflex bladder activity, firing on b ladder nerves and c-fos gene expression in spinal neurons was examined in urethane anesthetized female Wistar rats. The effect of DMSO (1-10 %) on nitric oxide release from urinary bladder strips or acutely diss ociated dorsal root ganglion cells was monitored in vitro with a porph yrinic microsensor, Results: DMSO acutely increased reflex firing of p elvic nerve efferent axons, decreased bladder capacity and also increa sed neuronal c-fos expression in spinal cord regions that exhibit c-fo s expression after chemical activation of capsaicin-sensitive bladder afferents. DMSO, like capsaicin, also directly released nitric oxide ( NO) from both dissociated dorsal root ganglion neurons and from isolat ed strips of urinary bladder. Conclusions: These results suggest that DMSO induced stimulation of bladder afferent pathways and NO release f rom afferent neurons may be a reflection of the initial event in the d esensitization of nociceptive pathways in the lower urinary tract (LUT ).