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. Su...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 μl 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 μl 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.展开更多
目的:探讨膀胱灌注辣椒辣素类似物(resiniferatoxin,RTX)治疗间质性膀胱炎(interstitial cystitis,IC)的有效性和安全性。方法:56例间质性膀胱炎患者行RTX一次性膀胱灌注治疗。观察用药前及用药后1周、1个月、3个月时患者的临床症状情况...目的:探讨膀胱灌注辣椒辣素类似物(resiniferatoxin,RTX)治疗间质性膀胱炎(interstitial cystitis,IC)的有效性和安全性。方法:56例间质性膀胱炎患者行RTX一次性膀胱灌注治疗。观察用药前及用药后1周、1个月、3个月时患者的临床症状情况(每日排尿次数、最大排尿容量、尿痛程度评分)和O′Leary-Sant间质性膀胱炎问卷表评分及生活质量评分(QOL)情况。并记录不良反应发生情况。结果:①患者用药后1周、1个月、3个月时每日排尿次数明显减少(用药前vs用药后1W、1M和3M的每日排尿次数:28.41±10.77 vs 15.30±4.77、15.63±3.70和17.19±4.06),最大排尿容量增加[用药前vs用药后1W、1M和3M的最大排尿容量为:124.26±79.31 vs 187.41±67.46、188.89±62.35和161.85±65.11(ml)],疼痛程度评分明显下降(用药前vs用药后1W、1M和3M的疼痛程度评分为:6.74±1.38 vs 3.89±1.15、4.63±1.31和4.85±1.67),与用药前相比,差异具有统计学意义。②患者用药后1周、1个月、3个月时O′Leary-Sant评分和生活质量评分与用药前相比(O′Leary-Sant评分:用药前vs用药后1W,1M,3M为27.93±4.03 vs 28.04±6.69,27.44±3.89,27.96±4.13;生活质量评分:用药前vs用药后1W、1M、3M为5.52±0.51 vs 5.30±0.47、5.33±0.56、5.44±0.51),比较差异无统计学意义。③所有患者均坚持完成试验,无一例退出。使用RTX后患者生命体征均平稳,其中20例有轻度或中度膀胱或尿道刺激症状,可以耐受,1~3天后均自行消失,无全身不良反应。结论:用RTX膀胱灌注治疗能有效缓解间质性膀胱炎的临床症状和改善其生活质量,且耐受性及安全性好。展开更多
文摘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 μl 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 μl 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.
文摘目的:探讨膀胱灌注辣椒辣素类似物(resiniferatoxin,RTX)治疗间质性膀胱炎(interstitial cystitis,IC)的有效性和安全性。方法:56例间质性膀胱炎患者行RTX一次性膀胱灌注治疗。观察用药前及用药后1周、1个月、3个月时患者的临床症状情况(每日排尿次数、最大排尿容量、尿痛程度评分)和O′Leary-Sant间质性膀胱炎问卷表评分及生活质量评分(QOL)情况。并记录不良反应发生情况。结果:①患者用药后1周、1个月、3个月时每日排尿次数明显减少(用药前vs用药后1W、1M和3M的每日排尿次数:28.41±10.77 vs 15.30±4.77、15.63±3.70和17.19±4.06),最大排尿容量增加[用药前vs用药后1W、1M和3M的最大排尿容量为:124.26±79.31 vs 187.41±67.46、188.89±62.35和161.85±65.11(ml)],疼痛程度评分明显下降(用药前vs用药后1W、1M和3M的疼痛程度评分为:6.74±1.38 vs 3.89±1.15、4.63±1.31和4.85±1.67),与用药前相比,差异具有统计学意义。②患者用药后1周、1个月、3个月时O′Leary-Sant评分和生活质量评分与用药前相比(O′Leary-Sant评分:用药前vs用药后1W,1M,3M为27.93±4.03 vs 28.04±6.69,27.44±3.89,27.96±4.13;生活质量评分:用药前vs用药后1W、1M、3M为5.52±0.51 vs 5.30±0.47、5.33±0.56、5.44±0.51),比较差异无统计学意义。③所有患者均坚持完成试验,无一例退出。使用RTX后患者生命体征均平稳,其中20例有轻度或中度膀胱或尿道刺激症状,可以耐受,1~3天后均自行消失,无全身不良反应。结论:用RTX膀胱灌注治疗能有效缓解间质性膀胱炎的临床症状和改善其生活质量,且耐受性及安全性好。