Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Urol. 2013 Jan;189(1):343-51. doi: 10.1016/j.juro.2012.08.189. Epub 2012 Nov 20.
Bladder pain is a debilitating symptom of many urological conditions. There is no generally effective treatment. Abnormal urothelial turnover is common to multiple disease states but the specific components of urothelial injury and the resulting molecular signals that lead to bladder pain are unknown. We examined mouse models of bladder injury induced by uropathogenic Escherichia coli, protamine sulfate (Sigma®) and bacterial lipopolysaccharide to identify cellular and molecular correlates underlying pain sensitization in response to the stimuli.
C57BL/6 female mice (Jackson Laboratory, Bar Harbor, Maine) were given intravesicular protamine sulfate, lipopolysaccharide or uropathogenic E. coli. The impact of each on nociception was determined by measuring the evoked visceromotor response to bladder distention 24 hours after inoculation. Levels of pyuria and tissue inflammation were examined by urinary cytology and tissue histology. Quantitative polymerase chain reaction and gene expression analysis were used to identify injury profiles associated with nociception.
Protamine sulfate treatment was significantly analgesic upon bladder distention. Protamine treated bladders did not show pyuria or extensive tissue damage. Protamine injury was associated with a global decrease in the expression of inflammation associated genes. In contrast, uropathogenic E. coli injury significantly increased the nociceptive response to bladder distention. Lipopolysaccharide treatment did not affect nociception. Finally, injury induced expression of inflammation associated genes correlated with nociceptive responses.
Protamine treatment of the bladder is analgesic and tissue protective, and it suppresses the inflammatory cytokine expression normally associated with nociception. Also, the injury modalities that result in differential tissue response patterns provide an innovative method for identifying mediators of visceral pain.
膀胱疼痛是许多泌尿科疾病的一种使人虚弱的症状。目前还没有普遍有效的治疗方法。异常的尿路上皮更新是多种疾病状态的共同特征，但导致膀胱疼痛的尿路上皮损伤的具体成分和由此产生的分子信号尚不清楚。我们检查了由尿路致病性大肠杆菌、鱼精蛋白硫酸盐（Sigma®）和细菌脂多糖诱导的小鼠膀胱损伤模型，以确定对这些刺激产生疼痛敏化的细胞和分子相关性。
C57BL/6 雌性小鼠（杰克逊实验室，缅因州巴港）给予膀胱内鱼精蛋白硫酸盐、脂多糖或尿路致病性大肠杆菌。接种后 24 小时，通过测量膀胱扩张引起的内脏运动反应来确定每种物质对痛觉的影响。通过尿细胞学和组织学检查来检测脓尿和组织炎症的程度。定量聚合酶链反应和基因表达分析用于鉴定与疼痛相关的损伤谱。
膀胱扩张时，鱼精蛋白硫酸盐处理具有明显的镇痛作用。鱼精蛋白处理的膀胱没有出现脓尿或广泛的组织损伤。鱼精蛋白损伤与炎症相关基因的表达整体下降有关。相比之下，尿路致病性大肠杆菌损伤显著增加了对膀胱扩张的痛觉反应。脂多糖处理不影响痛觉。最后，损伤诱导的炎症相关基因表达与痛觉反应相关。
膀胱鱼精蛋白处理具有镇痛和组织保护作用，并抑制与疼痛相关的炎症细胞因子表达。此外，导致不同组织反应模式的损伤方式为鉴定内脏疼痛的介质提供了一种创新方法。
