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.
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| Berkley, Karen J; McAllister, Stacy L; Accius, Briane E et al. (2007) Endometriosis-induced vaginal hyperalgesia in the rat: effect of estropause, ovariectomy, and estradiol replacement. Pain 132 Suppl 1:S150-9 |
| Nagabukuro, Hiroshi; Berkley, Karen J (2007) Influence of endometriosis on visceromotor and cardiovascular responses induced by vaginal distention in the rat. Pain 132 Suppl 1:S96-103 |
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| Berkley, Karen J; Rapkin, Andrea J; Papka, Raymond E (2005) The pains of endometriosis. Science 308:1587-9 |
