Improvement in Neurogenic Detrusor Overactivity by Peripheral C Fiber's Suppression With Cyclooxygenase Inhibitors

Purpose

Cyclooxygenase inhibitors decrease micturition frequency in animals with bladder inflammation but to our knowledge the influence of cyclooxygenase inhibitors on detrusor overactivity has not been investigated. We evaluated the effects, and the site and mechanism of action of cyclooxygenase inhibitors on detrusor overactivity induced by cerebral infarction.

Materials and Methods

Cerebral infarcted rats underwent cumulative intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560 (Sigma®), the selective cyclooxygenase-2 inhibitor rofecoxib (Kemprotec, Middlesbrough, United Kingdom) or the nonselective cyclooxygenase inhibitor FYO-750 hourly plus a single intravenous administration of SC-560, rofecoxib or SC-560 plus rofecoxib. To evaluate the site of action cerebral infarcted rats underwent single intracerebroventricular or intrathecal administration of FYO-750. To evaluate the mechanism of action FYO-750 was intravenously administered in diuretic rats or cerebral infarcted rats pretreated with resiniferatoxin.

Results

For cumulative administration SC-560 (0.3 mg/kg), rofecoxib (0.3 mg/kg) and FYO-750 (0.1 to 1 mg/kg) significantly increased bladder capacity. For single administration neither SC-560 (0.03 mg/kg) nor rofecoxib (0.03 mg/kg) affected bladder capacity but SC-560 plus rofecoxib significantly increased bladder capacity vs vehicle. Intracerebroventricular and intrathecal administration of FYO-750 did not affect bladder capacity. FYO-750 did not affect urinary production in diuretic rats and the effects of FYO-750 were blocked by resiniferatoxin except at the highest drug dose.

Conclusions

Results indicate that cyclooxygenase inhibitors improve detrusor overactivity caused by cerebral infarction by suppressing peripheral C fiber's without affecting urinary production. The nonselective cyclooxygenase inhibitor showed more potent efficiency than the selective cyclooxygenase-1 or the cyclooxygenase-2 inhibitor alone.

Key Words: urinary bladder, urinary bladder, overactive, nerve fibers, unmyelinated, cyclooxygenase inhibitors, rats, Sprague-Dawley

Abbreviations and Acronyms: BC, bladder capacity, CI, cerebral infarcted, CMG, cystometrography, COX, cyclooxygenase, DO, detrusor overactivity, ID, inner diameter, MCAO, middle cerebral artery occlusion, OD, outer diameter, PG, prostaglandin, RTX, resiniferatoxin, SO, sham operated, VV, voided volume