Uterus & Colon Influences on Bladder Function in Females

描述（由申请人提供）：在健康个体中，下尿路、胃肠道和生殖道的活动相互协调，以避免冲突。虽然这种多系统协调的机制还不清楚，但中枢和外周神经系统中有许多位置可能组织协调。这种内脏-内脏相互作用在健康中的存在提出了关于它们如何影响病理生理学体征和症状的问题。例如，子宫或结肠病变如何影响健康或患病膀胱的功能？虽然在这个问题上的研究一直很少，最近的研究表明，多系统相互作用确实可以对泌尿系统和其他盆腔器官病理生理学的体征和症状产生深远的影响，这种情况下，有相当大的诊断和治疗意义。这些最近的研究还表明，对这些体征和症状的另一个深刻影响是生殖状态（例如，卵巢周期性）。 因此，这项使用雌性大鼠的新研究计划的最终长期目标将是以一种有可能转化为临床的方式提高我们对这些影响及其机制的理解。这项为期两年的R21申请的目的是探索启动该计划的协议。提出了两组对麻醉雌性大鼠的研究。第一组将测试两个假设：（i）子宫或结肠的病理生理学影响健康膀胱的运动，以及（ii）影响随发情阶段而变化。对于这些研究，将使用经尿道膀胱测压法测量不同发情期大鼠子宫或结肠炎症（或假炎症）前后的排尿阈值。第二组将检验假设，即发炎的子宫（或结肠）和健康膀胱之间的相互作用需要输入到胸腰椎脊柱节段。在这些研究中，将在先前横断或假横断胸腰椎（T13-L2）背根的大鼠组中比较子宫（或结肠）炎症对排尿阈值的影响。这些探索性研究的结果将用于制定更长期的研究计划。

DESCRIPTION (provided by applicant): In healthy individuals, activities of the lower urinary, gastrointestinal, and reproductive tracts are coordinated with each other to avoid conflict. Although the mechanisms of this multisystem coordination are not well understood, there are many locations within the central and peripheral nervous systems where the coordination might be organized. The existence of such viscero-visceral interactions in health raises questions about how they might influence signs and symptoms of pathophysiology. For example, how does uterine or colon pathology affect functions of the healthy or diseased bladder? Although research on this issue has been scant, recent studies suggest that multisystem interactions can indeed exert profound influences on signs and symptoms of urological and other pelvic organ pathophysiology, a situation that has considerable significance for diagnosis and treatment. These recent studies have also shown that another profound influence on such signs and symptoms is reproductive status (e.g., ovarian cyclicity). Accordingly, the eventual long-term goal of this new research program using female rats will be to improve our understanding of these influences and their mechanisms in a manner that has potential for translating to the clinic. The aim of this two-year R21 application is to explore protocols to initiate this program. Two sets of studies on urethane-anesthetized female rats are proposed. The first set will test two hypotheses: (i) that pathophysiology in the uterus or colon influences motility of the healthy bladder, and (ii) that the influences vary with estrous stage. For these studies, transurethral cystometry will be used to measure micturition thresholds before and after inflammation (or sham inflammation) of the uterus or colon in rats in different estrous stages. The second set will test the hypothesis that the interactions between the inflamed uterus (or colon) and healthy bladder require input into thoracolumbar spinal segments. In these studies, the influence of uterine (or colon) inflammation on micturition thresholds will be compared in groups of rats with previously-transected or sham-transected thoracolumbar (T13-L2) dorsal roots. Results from these exploratory studies will be then be used to develop a longer program of research.