Stimulation mediated sensory enhancement of the urethral afferents

描述(申请人提供)：尿潴留是一种尿路疾病，使数十万人无法正常排空他们的膀胱内容物。尿潴留可能由许多原因引起，如自然衰老、急性创伤(尤其是在手术过程中)、糖尿病、多发性硬化症等。尽管原因多种多样，但大多数尿潴留病例的一个共同特征是，检测尿路液体流动的神经敏感度降低。这种敏感度的降低反过来又限制了自然控制膀胱排尿的反射的有效性。我们假设，通过使反射再次正常工作，提高尿路敏感度将缓解许多与滞留相关的症状。这项建议中的工作将证明有可能提高尿路敏感度。为了实现这一增强，我们将使用一种称为随机共振的过程，在该过程中，我们将亚阈值水平的电噪声(数量足够小，以至于感觉神经元无法检测到)直接注入到尿路中。这将在尿路的大鼠模型中完成。随机共振已经在其他生物感觉系统中取得了成功，我们假设这些不可检测的扰动将降低尿路感觉神经元的激活阈值，有效地提高它们对血流的敏感性。我们将通过阴部神经的记录来证明我们的发现，阴部神经将感觉信息从尿路传递到脊髓。我们将比较阴部神经在有和没有刺激的情况下对尿路液体流动的反应。我们可以得出结论，如果在有刺激的情况下观察到比没有刺激时更多的神经活动，那么敏感性就会增强，如果在刺激的情况下可以检测到较慢的流速，这也将作为敏感性增强的证据。最后，将结合动物实验建立下尿路随机共振的数学模型。这个模型将允许我们模拟许多不同类型的刺激和流量，以更好地指导动物的工作。使用该模型，我们可以研究广泛的实验参数，比我们使用生物系统进行测试的范围要多得多。我们将使用最佳刺激参数和流量的模型估计，以使我们自己有最大的成功机会来增强尿路敏感性。

DESCRIPTION (provided by applicant): Urinary retention is a disease of the urinary tract that prevents hundreds of thousands of people from properly emptying the contents of their bladder. Urinary retention can be caused by many things such as natural aging, acute trauma (especially during surgical procedures), diabetes, multiple sclerosis and others. Despite the range of causes, a feature common to most cases of urinary retention is a reduced neural sensitivity for detecting fluid flow in the urethra. This reduction in sensitivity, in turn, limits the effectivenes of reflexes that naturally control bladder voiding. We hypothesize that enhancing urethral sensitivity will mitigate many of the symptoms associated with retention by allowing the reflexes to once again function properly. The work in this proposal will demonstrate that it is possible to enhance urethral sensitivity. To accomplish this enhancement we will use a process called stochastic resonance, where we inject sub-threshold levels of electrical noise (amounts small enough that they cannot be detected by the sensory neurons) directly into the urethra. This will be done in a rat model of the urinary tract. Stochastic resonance has been successful in other biological sensory systems and we hypothesize that these undetectable perturbations will lower the activation threshold of the urethral sensory neurons, effectively increasing their sensitivity o flow. We will demonstrate our findings by recording from the pudendal nerve, which carries sensory information from the urethra to the spinal cord. We will compare the pudendal nerve's response to fluid flow in the urethra both with and without the stimulation at a range of flowrates We can conclude that sensitivity was enhanced if more neural activity is observed in the presence of the stimulation than without it, and if slower flowrates can be detected with the stimulation it will also serve as evidence of enhanced sensitivity. Finally, a mathematical model of stochastic resonance in the lower urinary tract will be developed in tandem with the animal experiments. This model will allow us to simulate many different types of stimulation and flowrates to better guide the animal work. Using the model we can investigate a wide range of experiment parameters, many more than we could test using the biological system. We will use the model estimates of the optimal stimulation parameters and flowrates to give ourselves the best chance of success for enhancing urethral sensitivity.