P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin
P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin
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DOI：
10.1016/j.eururo.2003.12.017
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发表时间：
2004-08-01
期刊：
影响因子：
23.4
通讯作者：
Anand, P
中科院分区：
文献类型：
--
作者：
Brady, CM;Apostolidis, A;Anand, P
目的：ATP门控嘌呤能受体P2 X3由小直径感觉神经元表达，并已在正常和神经源性人膀胱上皮下纤维中鉴定。动物模型显示，ATP在膀胱扩张期间由尿道鞘释放，表明P2 X3受体在正常膀胱功能中的机械感觉作用。成功治疗脊髓神经性逼尿肌过度活动（NDO）与膀胱内注射树脂毒素（RTX），其中部分作用于上皮下C纤维，提供了证据的C纤维介导的脊髓反射的出现。本研究的目的是探讨P2 X3阳性神经支配在这种病理性排尿反射的可能作用，通过比较上皮下P2 X3免疫反应性的控制和NDO患者的膀胱内RTX.Methods：膀胱活检获得8个对照组和20例难治性NDO患者参加了膀胱内RTX试验。P2 X3神经纤维的密度和强度进行了研究，在标本通过免疫组化。结果：P2 X3-IR神经纤维显着增加NDO患者相比，对照组（p = 0.014）。13例患者的RTX前后活检可用于免疫组织化学;其中5例临床反应，8例无反应。在5例患者谁响应RTX，有一个显着的减少P2 X3阳性纤维（p = 0.032），而在无反应者，P2 X3-IR神经纤维密度没有显着改变。结论：在NDO患者中，P2 X3-IR神经纤维的数量增加，在thuburothorax。有一个显着减少P2 X3免疫反应性的反应RTX，表明潜在的病理生理作用的P2 X3表达纤维。(C)2004 Elsevier B. V.保留所有权利。
Objectives: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX.Methods: Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry.Results: P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (p = 0.014). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p = 0.032), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly.Conclusions: In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres. (C) 2004 Elsevier B.V. All rights reserved.