Pregnancy increases excitability of mechanosensitive afferents innervating the uterine cervix

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

Spontaneous activity of afferents increases during pregnancy (A) and this is due primarily to an increase in spontaneous activity of low threshold afferents (B). Values are median ± 25^th and 75^th percentile (A) or + 75^th percentile (B) of 51 nonpregnant, 49 pregnant Day 17 and 51 pregnant Day 21 units. * P < 0.05 compared to nonpregnant # P < 0.05 compared to Day 17 pregnant

Figure 2

Effect of pregnancy on threshold to uterine cervical distension. A) The proportion of low threshold fibers (defined as those responding to 20 g distension) increases during pregnancy. B) Thresholds, with each fiber’s threshold indicated as a solid circle. * P < 0.05 compared to nonpregnant

Figure 3

A typical response to uterine cervical distension in a single fiber from a 21 day pregnant rat. B) Net nerve activity (elicited activity during distension minus activity in the absence of stimulation) during uterine cervical distension increases progressively during pregnancy. Values are mean ± SE of 51 nonpregnant, 49 pregnant Day 17 and 51 pregnant Day 21 units. * P < 0.05 compared to nonpregnant # P < 0.05 compared to Day 17 pregnant

Figure 4

Pregnancy increases the net nerve activity (elicited activity during distension minus activity in the absence of stimulation) during uterine cervical distension in low threshold fibers (A) but not in high threshold fibers (B). Values are mean ± SE of 30 nonpregnant, 39 pregnant Day 17, and 40 pregnant Day 21 low threshold fibers and 21 nonpregnant, 10 pregnant Day 17, and 11 pregnant Day 21 high threshold fibers. * P < 0.05 compared to nonpregnant # P < 0.05 compared to Day 17 pregnant

Figure 5

Illustration of the relationship between uterine cervical distension force and hypogastric nerve firing. A) Intrauterine pressure increases in a cyclical fashion with a frequency of approximately 1/min in the rat, resulting in peak pressures of approximately 15 mm Hg. Based on the spontaneous activity and stimulus response relationships observed in the current study, this increase in uterine cervical distension pressure results in nerve activity which is greater in the 21 day pregnant rat (B, thick line) than the nonpregnant rat (B, thin line). The cumulative firing of the hypothetical afferent over the 15 min period diverges over time, with greater activity in the pregnant than nonpregnant animal (C).