DMSO: effect on bladder afferent neurons and nitric oxide release.
OBJECTIVE
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 synthase 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 if DMSO can influence the release of nitric oxide in the bladder or from afferent neurons.


METHODS
The effects of intravesical DMSO (10% solution in saline) on reflex bladder activity, firing on bladder 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 dissociated dorsal root ganglion cells was monitored in vitro with a porphyrinic microsensor.


RESULTS
DMSO acutely increased reflex firing of pelvic nerve efferent axons, decreased bladder capacity and also increased neuronal c-fos expression in spinal cord regions that exhibit c-fos 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 isolated strips of urinary bladder.


CONCLUSIONS
These results suggest that DMSO induced stimulation of bladder afferent pathways and NO release from afferent neurons may be a reflection of the initial event in the desensitization of nociceptive pathways in the lower urinary tract (LUT).
Birder
L A
LA
Department of Pharmacology, University of Pittsburgh, Pennsylvania, USA.
Kanai
A J
AJ
de Groat
W C
WC
D000283:Administration, Intravesical; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002211:Capsaicin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use*; D005260:Female; D066298:In Vitro Techniques; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D016760:Proto-Oncogene Proteins c-fos; D009569:Nitric Oxide; D002211:Capsaicin; D004121:Dimethyl Sulfoxide