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The Role of Sensory Neurons in Cervical Ripening : Effects of Estrogen and Neuropeptides

C.N. Mowa and R.E. Papka

Department of Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio

Correspondence to: Dr. R.E. Papka, Northeastern Ohio Universities College of Medicine, Department of Neurobiology, 4209 State Rt. 44, P.O. Box 95, Rootstown, OH 44272. E-mail: rpapka{at}neoucom.edu

Central nervous system nuclei and circuits, such as the medial preoptic, ventromedial and paraventricular nuclei of the hypothalamus, play important roles in reproduction and parturition, and are influenced by estrogen. Peripheral autonomic and sensory neurons also play important roles in pregnancy and parturition. Moreover, the steroid hormone estrogen acts directly, not only on the reproductive tract organs (uterus and cervix), but also on the central and peripheral nerves by regulating expression of various neuronal genes. The peripheral primary afferent neurons innervating the uterine cervix relay mechanical and biochemical sensory information induced by local cervical events and by passage of fetuses, to the spinal cord and supraspinal centers. Consequently, the birth process in mammals is influenced by the combined action of neurons and hormones. Peripheral sensory stimuli, induced physiologically by fetal expulsion or mechanically by vaginocervical stimulation, alter behavior, as well as autonomic and neuroendocrine systems. Recent evidence indicates that primary afferent neurons innervating the cervix, in addition to their sensory effects, likely exert local "efferent" actions on the ripening cervix near term. These efferent effects may involve estrogen-regulated production of such neuropeptides as substance P and calcitonin gene-related peptide in lumbosacral dorsal root ganglia, and their release in the cervix. Collectively, these findings suggest an interrelationship among estrogen, cervix-related sensory neurons, and local cervical events near term.

(J Histochem Cytochem 52:1249–1258, 2004)

Key Words: cervical ripening • sensory nerves • substance P • calcitonin gene-related peptide • vascular endothelial growth factor • neuropeptides

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