Pregnancy Increases Excitability of Mechanosensitive Afferents Innervating the Uterine Cervix

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
Anesthesiology (Impact Factor: 5.88). 06/2008; 108(6):1087-92. DOI: 10.1097/ALN.0b013e31817302e0
Source: PubMed


Labor pain derives primarily from stimulation of afferents innervating the uterine cervix and lower uterine segment. The authors have previously shown that the excitability of these afferents is regulated by sex hormones and test in this study whether pregnancy also alters their excitability.
After animal care committee approval, Sprague-Dawley rats (nonpregnant, pregnant days 17 and 21) were anesthetized, and two metal rods were placed through the cervix for distension. The right hypogastric nerve was dissected and carefully teased until recording from a single unit was obtained. Spontaneous activity and the response to a graded distension (20-80 g) were recorded for off-line analysis.
A total of 151 fiber units were recorded. Pregnancy was associated with an increase in spontaneous nerve activity in the absence of a mechanical stimulus (median of 0.98 and 1.56 Hz from pregnant days 17 and 21, respectively, compared with 0.45 Hz in nonpregnant; P < 0.01). The proportion of fibers responding to the weakest stimulus (20 g) was significantly greater in pregnant than in nonpregnant animals. The response to graded distension differed significantly among groups, with day 21 > day 17 > nonpregnant.
Afferents that innervate the uterine cervix sprout into this tissue during late pregnancy, and estrogen increases excitability of these mechanosensitive afferents. Here, the authors show that excitability also increases during pregnancy. These data suggest that, close to the onset of labor, there is an increased input to the spinal cord from cervical distension and an increased depolarization of afferent terminals in the cervix, effects that could influence pain and the progress of labor.

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    • "In a model of mechanical stimulation of the uterine-cervix in rats to emulate labor, ovariectomy decreased the visceromotor response which was reversed by E2 replacement and the response of the innervating hypogastric nerve afferents increased in OVx+E2 rats via activation of TRPV1 (Liu et al., 2005; Yan et al., 2007). Correspondingly , uterine-cervix afferent activity increased as estrogen levels increased during pregnancy (Liu et al., 2008). NMDA receptor activity could partially account for the sex difference induced by estrogen in deep tissue pain. "
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    ABSTRACT: In contrast to the uterus, the cervix is well innervated during pregnancy and the density of nerve fibers increases before birth. To assess neural connections between the cervix and the spinal cord, the cervix of pregnant mice was injected with the trans-synaptic retrograde neural tract tracer pseudorabies virus (PRV). After 5 days, the virus was present in nerve cells and fibers in specific areas of the sensory, autonomic, and motor subdivisions of the thoracolumbar spinal cord. In nonpregnant controls, the virus was predominantly distributed in laminae I-III in the dorsal gray sensory areas with the heaviest label in the substantia gelatinosa compared with the autonomic or motor areas. Labeled cells and processes were sparse in other regions, except for a prominent cluster in the intermediolateral column (lamina VII). Photomicrographs of spinal cord sections were digitized, and the total area with the virus was estimated. Compared with nonpregnant controls, the area with PRV was significantly decreased in all the spinal cord subdivisions in pregnant mice except in the intermediolateral column. However, areas with the virus were equivalent in mice injected with PRV at 4 days or 1 day before birth. These findings suggest that the predominant innervation of the murine cervix is from the sensory regions of the thoracolumbar spinal cord, and that these connections diminish with pregnancy. The results raise the possibility that the remaining connections from sensory and autonomic subdivisions, particularly the intermediolateral column, of the thoracolumbar spinal cord may be important for increased density of nerve fibers in the cervix as pregnancy nears term.
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    ABSTRACT: The present review highlights recent findings focusing on effects on the cervical innervation exerted by term pregnancy and labour. The corpus uteri is almost denervated in term pregnancy, as demonstrated in both humans and rodents, whereas the cervical innervation remains dense throughout pregnancy and labour. In rats, fewer connections between sensory subdivisions in spinal cord segments and the cervix have been observed in late pregnancy as compared with the nonpregnant state. In term pregnancy an increased excitability of mechanosensitive afferents innervating the cervix has been demonstrated. The reasons for these seemingly contradictory findings may be clarified in further studies. Transient receptor potential vanilloid receptor, a key molecule in nociception, has been identified in the human cervix uteri in the nonpregnant state and during pregnancy and labour as opposed to the corpus, in which transient receptor potential vanilloid receptor disappears during pregnancy. These findings add evidence to the hypothesis that the uterine cervix is the main site from where labour pain propagates. The conservation of the cervical innervation in term pregnancy and labour, in contrast to the corpus, and the large number of mediators involved in cervical ripening clearly indicate that the cervix plays a crucial role in pregnancy maintenance, labour initiation, labour pain and parturition.
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