Influence of endometriosis on visceromotor and cardiovascular responses induced by vaginal distention in the rat

Abstract

This study examined pseudoaffective responses elicited by vaginal distention in urethane-anesthetized rats, and tested hypotheses that responses would be increased by endometriosis (ENDO) and vary with the estrous cycle. Three groups were studied: ENDO, shamENDO, and Naive. ENDO was induced by autotransplanting small pieces of uterine horn (or, for shamENDO, fat) on mesenteric arteries. Ten weeks later, rats in proestrus or metestrus were anesthetized with urethane. Distendable latex balloons were inserted into the vaginal canal. While an increasing series of vaginal distentions was delivered, changes in electromyographic activity of the external oblique musculature (visceromotor response, VMR) and mean arterial pressure (pressor) responses were simultaneously measured. Vaginal distention produced VMR and pressor responses in all groups. These responses were significantly greater in ENDO than in the other groups, and greater in proestrus than metestrus. Although the overall amount of cystic tissue was greater in proestrous than metestrous rats, there was no correlation between these amounts and VMR or pressor responses. Acute spinalization (T8-T9) and bilateral pelvic, but not hypogastric, neurectomy attenuated both VMR and pressor responses, supporting the hypothesis that vaginal nociception involves suprathoracic spinal processing of information conveyed by the pelvic nerve. These effects on VMR and pressor responses to vaginal distention parallel behavioral escape responses to the same stimuli reported previously. The findings encourage continued use of VMR and pressor responses for further investigation of mechanisms underlying pain associated with ENDO and its potential treatment.

Figure 1

Influence of estrous stage on VMR and pressor responses to vaginal distention in Naïve rats. A is a representative example of results from a single Naïve rat in metestrus during increasing volumes of distention of the vaginal canal. This example shows traces of the abdominal EMG, the number of spikes of the EMG, the mean arterial pressure (MAP) and the pressure of the vaginal balloon (uncorrected, see Methods). B compares changes in the MAP from the baseline MAP in proestrus and metestrus during different volumes of vaginal distention. C compares changes in the VMR in proestrus and metestrus during different volumes of vaginal distention. These changes were calculated after setting the response to a 1.3 ml vaginal distention volume as 100%. D compares the vaginal pressure (“tone,” corrected for pressure within the balloon, see Methods) in proestrus and metestrus produced by different volumes of vaginal distention. Each plot displays mean ± S.E.M. There were no significant estrous differences in any measure.

Figure 2

Representative examples similar to the one shown in Fig. 1A, here showing the effects on VMR and pressor responses to distention of the vaginal canal of acute spinalization (A), bilateral pelvic neurectomy (B) or bilateral hypogastric neurectomy (C). The interval between spinalization (arrow in A) and remeasurement of the VMR and pressor responses was > 30 min in all cases. The interval between neurectomy (arrows in B and C) and remeasurement of the VMR and pressor responses was > 15 min in all cases.

Figure 3

Effects of ENDO on VMR (A,D), pressor (B,E) responses, and vaginal tone (C,F) in proestrus (A, B, C) and metestrus (D, E, F) to different volumes of vaginal distention. See legend in Fig. 1 for details. The asterisks on each graph show, for each group, the lowest volume at which the response was signficantly greater than the response to the smallest distention volume (i.e., the response “threshold”). The bar graphs inserted in A, B, D and E show differences in the AUC between the Naïve group and the shamENDO or ENDO groups. Asterisks over the bars indicate that the AUC of that group differed signficantly from AUC for the Naïve group (*, P > 0.05; **, P > 0.01).

Figure 4

Correlation between cyst burden and the VMR or pressor response in ENDO rats. Graphs are scatterplots containing trendlines comparing cyst buden and AUC values for VMR (A) or MAP (B). Values for rats in proestrus are shown as filled squares; values for rats in metestrus are shown as unfilled squares. Note that although the cyst burden was greater for proestrous than metestrous rats, there was no significant correlation between the values for rats in either stage (or all rats).