Inhibitory effect of intravesically applied botulinum toxin A in chronic bladder inflammation

We evaluated a putative inhibitory effect of intravesical botulinum toxin A (BTX-A) on afferent pathways in conditions of chronic bladder inflammation.

Female Sprague-Dawley rats were divided into 4 groups, namely group 1-saline treated, group 2-BTX-A treated, group 3-cyclophosphamide (CYP) treated and group 4-BTX-A and CYP treated. At the beginning of the treatment period all animals received intravesical protamine sulfate (1%), followed by intravesical BTX-A or saline. Subsequently CYP or saline was injected intraperitoneally every 3 days for 10 days. The rats then underwent cystometrogram evaluation prior to spinal cord harvest. Sections from the L6 and S1 spinal cord segments were examined for the total number of Fos immunoreactive cells.

Comparisons of the L6 and S1 sections showed a significant difference among groups (p <0.05). CYP treated animals had a significant increase in L6 and S1 (78% and 107%, respectively) c-fos expression compared with saline controls (p <0.001). Comparison of the CYP and BTX-A/CYP groups showed a significant decrease in L6 and S1 in c-fos expression (50% and 52%, respectively) in the BTX-A/CYP treated group (p <0.001). No significant difference was present between the saline and BTX-A alone groups. Cystometrogram studies revealed that the nonvoiding intercontractile interval increased by more than 10-fold in BTX-A/CYP treated animals compared with CYP treated rats (p <0.01).

In a CYP model of chronic bladder inflammation intravesical BTX-A significantly inhibits the afferent neural response without impairing efferent bladder function.