A developing view of the origins of urgency: the importance of animal models
A developing view of the origins of urgency: the importance of animal models
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对紧迫性起源的不断发展的看法：动物模型的重要性
DOI：
10.1111/j.1464-410x.2005.05652.x
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发表时间：
2005
影响因子：
4.5
通讯作者：
J. Gillespie
中科院分区：
文献类型：
--
作者：
J. Gillespie
虽然在将动物数据应用于人类生理学时应该谨慎，但如果注意区分一般原理和细节的复杂性，特别是对被检查的物种，那么在动物模型上的实验可以揭示膀胱中的基本现象，为急症的起源提供线索。最近来自豚鼠整个离体膀胱的数据显示了排尿周期充血期自主活动的意外复杂性：膀胱内压力的小而短暂的增加与收缩活动的传播波和膀胱壁的局部伸展有关。这种复杂的、协调的活动表明，膀胱壁内存在专门用于产生相活动的机制。因此，似乎有两个系统控制逼尿肌收缩：一个与类似排尿收缩的整体收缩有关，另一个产生相性活动。产生相活动的机制似乎是兴奋性和抑制性输入的复杂整合点。有证据表明，膀胱壁的局部活动产生传入放电，这可能有助于膀胱感觉。动物数据表明，一种新的运动/感觉系统包含收缩（运动）事件，引起拉伸，从而激活传入神经（感觉）。该系统的运动元件似乎以一种高度复杂的方式控制，因此运动活动的幅度和频率可以通过各种输入来调节。这就提出了一种可能性，即该系统告知中枢神经系统的敏感性，从而在排尿周期中对膀胱状态的感知，可以通过针对膀胱过度活动区域（包括急迫性尿失禁）的新型药物来控制。
Although caution should be used when applying animal data to human physiology, if care is taken to differentiate between general principles and complications of detail, particular to the species being examined, then experimentation on animal models can reveal basic phenomena in the bladder that offer clues to the origin of urgency. Recent data from the whole isolated bladder of guinea pigs showed unexpected complexities in autonomous activity during the filling phase of the micturition cycle: small, transient increases in intravesical pressure were associated with propagating waves of contractile activity and localized stretches of bladder wall. This complex, coordinated activity suggests that there are mechanisms within the bladder wall devoted specifically to generating phasic activity. Thus, there appear to be two systems controlling detrusor contractions: one associated with overall contractions similar to the micturition contraction and the other generating phasic activity. The mechanisms generating the phasic activity appear to be the point of complex integration of both excitatory and inhibitory inputs. There is evidence that local activity in the bladder wall generates afferent discharge, which probably contributes to bladder sensations. Animal data suggest a novel motor/sensory system incorporating contractile (motor) events, which cause stretches resulting in activation of afferent nerves (sensory). The motor element of this system appears to be controlled in a highly complex fashion such that the amplitude and frequency of the motor activity can be modulated by a variety of inputs. This raises the possibility that the sensitivity of the system informing the central nervous system, and thus awareness of the bladder's state during the micturition cycle, can be manipulated, possibly via novel drugs targeted at areas involved in overactive bladder, including urgency incontinence.