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Detrusor Underactivity Model in Rats by Conus Medullaris Transection
Published on: August 28, 2020
Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats
Osamu Yokoyama1, Anwar Yusup, Yoshiji Miwa
1Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. oyoko@fmsrsa.fukui-med.ac.jp
Purpose:
We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.
Materials And Methods:
To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated.
Results:
Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats.
Conclusions:
These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.
Insights
Low-dose tolterodine improves bladder capacity by inhibiting C-fiber bladder afferent nerves. This effect is dependent on intact C-fiber function, as suppression of these nerves with resiniferatoxin (RTX) abolished tolterodine
Area of Science:
- Neuroscience
- Urology
- Pharmacology
Background:
- C-fiber bladder afferent nerves play a crucial role in bladder function and sensation.
- Antimuscarinic agents like tolterodine are used to treat overactive bladder, but their precise mechanism of action, particularly concerning C-fibers, requires further elucidation.
- Cerebral infarct can lead to altered bladder function, necessitating investigation into therapeutic interventions.
Purpose of the Study:
- To investigate whether the therapeutic effects of tolterodine on bladder capacity are contingent upon the functional integrity of C-fiber bladder afferent nerves.
- To determine the influence of C-fiber suppression on the efficacy of tolterodine administered intravenously and intravesically.
Main Methods:
- Female Sprague-Dawley rats underwent subcutaneous resiniferatoxin (RTX) injection to desensitize C-fiber bladder afferent nerves, or received vehicle control.
- Middle cerebral artery occlusion (MCAO) was performed to induce cerebral infarct (CI).
- Cystometrography was conducted to assess bladder capacity and function following intravenous or intravesical administration of varying tolterodine doses in RTX-treated and vehicle-treated rats with CI.
Main Results:
- In vehicle-treated rats with cerebral infarct (VEH-CI), low-dose tolterodine significantly increased bladder capacity (BC) without affecting residual volume.
- In contrast, tolterodine had no significant effect on BC in RTX-treated rats with cerebral infarct (RTX-CI), indicating C-fiber dependence.
- High-dose tolterodine decreased bladder contraction pressure and increased residual volume in both VEH-CI and RTX-CI rats, suggesting a dose-dependent, potentially non-specific effect.
Conclusions:
- Low-dose tolterodine appears to exert its beneficial effect on bladder capacity by inhibiting C-fiber bladder afferent nerves.
- The findings suggest that intact C-fiber nerve function is essential for tolterodine to improve bladder storage during the storage phase.
- This study highlights a specific mechanism by which antimuscarinic agents may improve bladder function, particularly in conditions involving altered afferent signaling.
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