Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome
Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome
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DOI：
10.1016/j.juro.2016.06.089
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发表时间：
2017-01-01
影响因子：
6.6
通讯作者：
Viereck, Volker
中科院分区：
文献类型：
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作者：
Regauer, Sigrid;Gamper, Marianne;Viereck, Volker
目的：疼痛是区分膀胱疼痛综合征/间质性膀胱炎与膀胱过度活动症的关键症状，但存在重叠。为了找到这些膀胱疾病的鉴别标记，我们检测了膀胱活检中感觉神经支配和神经营养因子受体的表达以及尿液中神经生长因子的水平。材料和方法：膀胱疼痛综合征/间质性膀胱炎患者的膀胱活检，包括12例有Hunner病变和19例无Hunner病变，13例膀胱过度活动综合征和12例健康对照，通过免疫组织化学用针对神经细胞标记物PGP9.5（神经元特异性蛋白基因产物9.5）、p75（NTR）（p75神经营养因子受体）、B淋巴细胞标记物CD 20和肥大细胞类胰蛋白酶的抗体进行分析。采用酶联免疫吸附试验定量测定尿神经生长因子。PGP9.5染色上皮下感觉神经支配的敏感性为97%，特异性为76%，淋巴细胞浸润增加的敏感性为90%，特异性为80%，和尿路上皮缺损对区分膀胱疼痛综合征的敏感性为97%，特异性为76%。间质性膀胱炎伴和不伴Hunner病变的膀胱过度活动综合征和健康对照。感觉神经支配增加与粘膜下肥大细胞定位有关。基底尿路上皮细胞中p75（NTR）染色提示膀胱疼痛综合征/间质性膀胱炎。尿神经生长因子水平低于检测水平，并没有区分膀胱疾病从健康controls.Conclusions：感觉神经支配和基底尿路上皮p75（NTR）染色与炎症淋巴细胞和尿路上皮完整性的评估允许分化膀胱疼痛综合征/间质性膀胱炎和膀胱过度活动症综合征，即使在没有Hunner病变。此外，这些组织病理学标准能够识别早期疾病阶段或无症状/无症状病例，并可能允许及时治疗以防止疾病进展。
Purpose: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine.Materials and Methods: Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75(NTR) (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay.Results: Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75(NTR) in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls.Conclusions: Sensory hyperinnervation and basal urothelial p75(NTR) staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.