Two important problems in obstetrics are control of uterine body contractions and cervical dilatation. The long-term goal of this research is to understand neural mechanisms for integration of uterine cervical information and how these play a role in cervical ripening and parturition (act of giving birth) - particularly as this relates to pre-term or protracted labor, spinal cord-injured females and autonomic dysreflexia. Rationale for these studies is that birthing problems are critical obstetric problems; pre-term labor occurs in 5-10 percent of pregnancies in North America. Within this context, the aims of this proposal are to elucidate the sensory neural substrate of the uterine cervix and how this substrate relates to physical changes in the cervix during cervical ripening and parturition. We propose that this substrate involves sensory nerves, neurotransmitters, receptors, the hormone estrogen, and controlled neurogenic inflammation and leads to the hypothesis: sensory neurons and transmitters innervating the uterine cervix are estrogen responsive, plastic, and are critical components participating in tissue rearrangements occurring at cervical ripening and parturition.
Specific aims will determine: 1) if there is enhanced synthesis and release of neurotransmitters by sensory neurons innervating the uterine cervix, specifically at cervical ripening & parturition; 2) if there are specific neurochemically identifiable sensory neurons of lumbosacral spinal ganglia activated expressly at cervical ripening and parturition; 3) if estrogen, working through estrogen receptors, influences levels of neurotransmitters in sensory ganglionic neurons innervating the cervix during pregnancy, parturition, and early postpartum; 4) if cervical ripening and parturition entail a controlled neurogenic inflammatory process; and 5) if specific subclasses of small C-type (peptidergic and non-peptidergic) neurons have identifiable roles in cervical ripening and parturition. These studies will utilize in situ hybridization, RT-PCR, Western blots, immunohistochemistry, nerve transections and neurotoxins. Health benefits from understanding involvement of neural mechanisms in the uterine cervix include an increased basic understanding of neuroendocrine coordination of gestational events including pregnancy, cervical ripening and parturition and the possibility of remediating problems such as pre-term labor, protracted labor, and autonomic dysreflexia. Finally, knowledge of estrogen responsive sensory neurons has important implications for understanding neuropathic pain syndromes influenced by estrogen levels.
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