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


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.
Department of Urology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China. chuang82@ms26.hinet.net
Yao-Chi
YC
Chuang
Naoki
N
Yoshimura
Chao-Cheng
CC
Huang
Moya
M
Wu
Po-Hui
PH
Chiang
Michael B
MB
Chancellor
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D002211:Capsaicin; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D015552:Injections, Intralesional; D008159:Lumbar Vertebrae; D008297:Male; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D011336:Probability; D011472:Prostatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000187:drug effects
D018836:Inflammation Mediators; D051546:Cyclooxygenase 2; D019274:Botulinum Toxins, Type A; D002211:Capsaicin