Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat

J Urol. 2008 Aug;180(2):742-8. doi: 10.1016/j.juro.2007.07.120. Epub 2008 Jun 13.


Purpose: 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.

Materials and methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / administration & dosage*
  • Capsaicin
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Inflammation Mediators / analysis
  • Inflammation Mediators / metabolism*
  • Injections, Intralesional
  • Lumbar Vertebrae
  • Male
  • Pain / physiopathology
  • Pain / prevention & control*
  • Pain Measurement
  • Probability
  • Prostatitis / chemically induced
  • Prostatitis / drug therapy*
  • Prostatitis / enzymology*
  • Prostatitis / pathology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Sensitivity and Specificity
  • Spinal Cord / drug effects


  • Inflammation Mediators
  • Cyclooxygenase 2
  • Botulinum Toxins, Type A
  • Capsaicin