Mechanisms involved in new therapies for overactive bladder
Mechanisms involved in new therapies for overactive bladder
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DOI：
10.1016/j.urology.2003.11.001
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发表时间：
2004-03-01
期刊：
影响因子：
2.1
通讯作者：
Cruz, F
中科院分区：
文献类型：
--
作者：
Cruz, F
在过去的几年中，香草类物质和肉毒杆菌-A 毒素作为膀胱过度活动症的新疗法被广泛研究。对于神经源性和非神经源性逼尿肌过度活动患者，膀胱内注射辣椒素或树脂毒素（香草素家族成员 2）已被证明可以增加膀胱容量并减少急迫性尿失禁。此外，香草素还被证明可以减轻过敏性疾病患者的膀胱疼痛。香草酸是 1 型香草酸受体 (VR1) 的外源配体，VR1 是存在于 C 型初级传入神经纤维膜中的离子通道。这种受体在疼痛感知和排尿反射控制中发挥着关键作用，可能会被神经生长因子（NGF）上调，神经生长因子是一种在过度活跃的逼尿肌组织中检测到的高浓度神经营养分子。香草酸通过减少感觉神经元对 NGF 的摄取，可能会抵消 VR1 的上调。膀胱内注射肉毒杆菌-A 毒素（一种由肉毒杆菌产生的神经毒素）被证明可以增加膀胱容量并减少神经源性逼尿肌过度活动患者的急迫性尿失禁发作。 A型肉毒杆菌毒素阻碍神经肌肉接头处胆碱能神经末梢释放乙酰胆碱，导致逼尿肌平滑肌麻痹。
During the last few years, vanilloid substances and botulinum-A toxin were extensively investigated as new therapies for overactive bladder. Intravesical administration of capsaicin or resiniferatoxin-2 members of the vanilloid family-has been shown to increase bladder capacity and decrease urge incontinence in patients with neurogenic, as well as nonneurogenic, forms of detrusor overactivity. In addition, vanilloids have been shown also to reduce bladder pain in patients with hypersensitive disorders. Vanilloids are exogenous ligands of vanilloid receptor type 1 (VR1), an ion channel present in the membrane of type C primary afferent nerve fibers. This receptor, which plays a key role in pain perception and control of the micturition reflex, may be upregulated by nerve growth factor (NGF), a neurotrophic molecule detected in high concentrations in overactive detrusor tissue. Vanilloids, by reducing uptake of NGF through sensory neurons, may counteract VR1 upregulation. Intravesical injections of botulinum-A toxin, a neurotoxin produced by Clostridium botulinum, were shown to increase bladder capacity and to decrease urge incontinence episodes in patients with neurogenic detrusor overactivity. Botulinum-A toxin impedes the release of acetylcholine from cholinergic nerve endings at the neuromuscular junction, leading to paralysis of the detrusor smooth muscle.