Intraprostatic Botulinum Toxin A Injection Inhibits Cyclooxygenase-2 Expression and Suppresses Prostatic Pain on Capsaicin Induced Prostatitis Model in Rat

Abstract

Cyclooxygenase-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins, which are important mediators of inflammation and pain. We investigated the effect of intraprostatic botulinum toxin A administration on pain reaction and cyclooxygenase-2 expression in a capsaicin induced prostatitis model in rats. Adult male Sprague-Dawley rats were injected with vehicle or capsaicin (10 mM, 0.1 cc) into the prostate. The nociceptive effects of capsaicin were evaluated for 30 minutes using a behavior approach. The prostate and L6 spinal cord were then removed for histology and cyclooxygenase-2 expression using Western blotting or immunostaining. A second set of animals was injected with botulinum toxin A (5 to 20 U) into the prostate 1 week before intraprostatic injection of capsaicin. Capsaicin induced increased pain behavior and inflammatory reaction. Botulinum toxin A 1 week before treatment dose dependently decreased inflammatory cell accumulation, cyclooxygenase-2 expression and prostatic pain. Botulinum toxin A (20 U) significantly decreased inflammatory cell accumulation, and cyclooxygenase-2 expression in the prostate, ventral horn and dorsal horn of the L6 spinal cord (93.5%, 89.4%, 90.5% and 77.5%, respectively). It decreased pain behavior for eye and locomotion scores (59.5% and 40.0%, respectively). Intraprostatic capsaicin injection activates cyclooxygenase-2 expression in the prostate, and spinal sensory and motor neurons, and it induces prostatic pain. Botulinum toxin A pretreatment could inhibit capsaicin induced cyclooxygenase-2 expression from the peripheral organ to the L6 spinal cord and inhibit prostatic pain and inflammation. This finding suggests a potential clinical benefit of botulinum toxin A for the treatment of nonbacterial prostatitis.