Intrathecal administration of resiniferatoxin produces analgesia against prostatodynia in rats.
BACKGROUND
Prostatodynia remains a difficult clinical problem. Resiniferatoxin (RTX), an ultrapotent vanilloid, can produce a selective and long-lasting desensitization of nociception via C-fiber sensory neurons. Substance P (SP) and calcitonin gene-related peptide (CGRP) released from C-fibers are key neurotransmitters in visceral pain. In this study, we evaluated the analgesic effect of intrathecal RTX on rat prostatodynia.


METHODS
Male Sprague-Dawley rats were divided into 3 groups for different treatment. In group A, sham operation was preformed. In group B, 100 microl complete Freund's adjuvant (CFA) was injected into the rat's bilateral ventral prostate to induce chronic inflammation. In group C, after prostatitis formed, 50 microl 10 nmol/L RTX was injected into the rat's lumbosacral (L5-S2) vertebral canal. SP and CGRP contents in the spinal cord were investigated by immunohistochemistry and radioimmunoassay (RIA). Their transcriptional levels in dorsal root ganglion (DRG) were determined by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, pelvic nerve afferent discharge was recorded to explore the neuro-electrophysiological mechanisms underlying RTX-induced effect.


RESULTS
SP and CGRP released in the spinal cord and their synthesis in DRG were increased significantly in response to CFA-induced chronic prostatitis, whereas this increase was effectively inhibited by intrathecal RTX. Meanwhile, pelvic nerve afferent electrical activity was enhanced significantly in rats with chronic prostatitis, but it was attenuated markedly in RTX-treated rats paralleled by the change of neuropeptides.


CONCLUSIONS
Intrathecal RTX administration could produce an analgesic effect on rat prostatodynia. Suppression of pelvic nerve afferent electrical activity may be a crucial mechanism underlying RTX-induced analgesia. RTX intrathecal application may present a novel analgesic strategy of prostatodynia.
Tang
Wei
W
Urological Research Institute of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China.
Song
Bo
B
Zhou
Zan-Song
ZS
Lu
Gen-Sheng
GS
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000235:genetics; D004224:Diterpenes / Q000008:administration & dosage*; D007278:Injections, Spinal; D008297:Male; D011472:Prostatitis / Q000188:drug therapy*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000032:analysis / Q000235:genetics
D000700:Analgesics; D004224:Diterpenes; D012333:RNA, Messenger; D013373:Substance P; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide