Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve

Abstract

-Central nervous system neurons process information converging from the uterus, colon, and bladder, partly via the hypogastric nerve. This processing is influenced by the estrous cycle, suggesting the existence of an estrous-modifiable central nervous system substrate by which input from one pelvic organ can influence functioning of other pelvic organs. Here, we tested predictions from this hypothesis that acute inflammation of colon, uterine horn, or bladder would produce signs of inflammation in the other uninflamed organs (increase vascular permeability) and that cross-organ effects would vary with estrous and be eliminated by hypogastric neurectomy (HYPX). Under urethane anesthesia, the colon, uterine horn, or bladder of rats in proestrus or metestrus, with or without prior HYPX, was treated with mustard oil or saline. Two hours later, Evans Blue dye extravasation was measured to assess vascular permeability. Extravasation was increased in all inflamed organs, regardless of estrous stage. For rats in proestrus, but not metestrus, either colon or uterine horn inflammation significantly increased extravasation in the uninflamed bladder. Much smaller cross-organ effects were seen in colon and uterine horn. HYPX reduced extravasation in the inflamed colon and inflamed uterine horn, but not the inflamed bladder. HYPX eliminated the colon-to-bladder and uterine horn-to-bladder effects. These results demonstrate that inflaming one pelvic organ can produce estrous-modifiable signs of inflammation in other pelvic organs, particularly bladder, and suggest that the cross-organ effects involve the hypogastric nerve and are at least partly centrally mediated. Such effects could contribute to cooccurrence and cyclicity of distressing pelvic disorders in women. pelvic pain; inflammation; interstitial cystitis; uterus; colon NEURAL COORDINATION AND decision-making for many physiological and behavioral functions depends on convergence within the nervous system of information from different bodily regions (for example, see Ref 4). Such is the case, for example, in the control of walking, balance, posture, eye movements, blood pressure, fight/flight responses, and other sensorimotor functions (39). Much of this convergence involves heterotopic interactions between different somatic structures (muscles/ skin) or between somatic and visceral structures.Such coordination is less well understood between different internal organs; that is, viscerovisceral interactions. Studies have shown, however, that neurons in the spinal cord, dorsal column nuclei, solitary nucleus, medullary reticular formation, and thalamus process information that converges from different internal organs located in different functional systems, i.e., the reproductive, gastrointestinal, and urinary tracts (8,9,11,17,24,31,32,37,57,58,59,60). In some regions, this processing is robustly influenced by the estrous cycle and hormone manipulations (15,16).This cross-system, viscerovisceral convergence supports the concept that the nervous system provides a dynamic ...

Organ cross talk modulates pelvic pain

“…For example, mustard oil administered to the uterine horn or colon in female rats induced vascular permeability in the bladder consistent with inflammation at a site distinct from the inflammatory stimulus (41). This cross talk is at least partially bidirectional, because bladder irritation also sensitized the colon to distension stimuli (28), and this noxious effect can be mediated by either chemical or mechanical stimuli (11,34,35).…”

Spinal neurons activated in response to pudendal or pelvic nerve stimulation in female rats

“…In addition, coordination of muscle relaxation and contraction and vasodilatation and vasoconstriction, takes place during sexual behavior and voiding reflexes. The communication of sensory information with coordination of the appropriate autonomic and motor output takes place at multiple levels of the nervous system including the dorsal root ganglia, spinal cord and the brain [4,55,56,68]. The present study reports the spinal cord regions that may relay cross communication between the viscera and somatomotor systems in the lumbosacral spinal cord.…”

“…A number of studies have provided evidence for cross organ interactions between gastrointestinal, bladder and reproductive pelvic organs particularly examining the responses of different organs to inflammation of a single organ such as the bladder, uterine horn or colon [56,68]. In addition, coordination of muscle relaxation and contraction and vasodilatation and vasoconstriction, takes place during sexual behavior and voiding reflexes.…”

Convergence and cross talk in urogenital neural circuitries

“…This convergence, along with different MRF neuronal responses to urinary and sexual inputs, also creates the potential for cross-organ sensitization centrally. Cross talk between organs is an area of research that has been receiving increasing attention, as it likely explains why some individuals with irritation in one pelvic/visceral organ experience referred pain or altered sensations in unaffected viscera (Alagiri et al 1997;Dmitrieva and Berkley 2002;Malykhina et al 2006;Pezzone et al 2005;Qin et al 2005;Theoharides et al 2008;Winnard et al 2006). MRF neurons are well placed to be a potential site for central cross-organ sensitization.…”