The visceromotor response to colorectal distention fluctuates with the estrous cycle in rats

Abstract

The existence of a sex difference in several chronic pain syndromes and the fluctuation of symptoms during the menstrual cycle strongly suggest sex hormones are involved in pain processing. The mechanisms underlying these changes are not well understood. Using the colorectal distention model in the rat, we previously reported a sex difference in the response to distention [Ji Y, Murphy AZ, Traub RJ (2006) Sex differences in morphine induced analgesia of visceral pain are supraspinally and peripherally mediated. Am J Physiol Regul Integr Comp Physiol 291:R307-R314] and that ovariectomy decreased the responses to distention while estrogen replacement reversed the decrease [Ji Y, Murphy AZ, Traub RJ (2003) Estrogen modulates the visceromotor reflex and responses of spinal dorsal horn neurons to colorectal stimulation in the rat. J Neurosci 23:3908-3915], suggesting estrogen increases visceral nociception. In the present study we tested the hypothesis that the visceromotor response to colorectal distention fluctuates with the estrous cycle. Three measurements (vaginal smears, uterine tube weight and plasma estrogen concentration) were used to determine the estrous phase. Comparison of the visceromotor response threshold and magnitude was made between proestrus and metestrus/diestrus. Our experiment demonstrated that the distention threshold was significantly lower in proestrus (median: 15 mm Hg) as compared with metestrus/diestrus (median: 25 mm Hg); and the magnitude of the visceromotor response to graded intensities of colorectal distentions (20, 40, 60, 80 mm Hg) was significantly higher in proestrus. The results indicate that the visceromotor response fluctuates with estrous phase, providing evidence for endogenous estrogen modulation of visceral nociceptive processing that could contribute to sex differences.

Figure 1

Representative photomicrographs showing smears from rats in metestrus/diestrus, proestrus and estrus. A: Metestrus is characterized by the appearance of small leukocytes, mixed with round or irregular shaped nucleated or squamous epithelial cells in a vaginal smear. B: Diestrus smear has fewer leukocytes mixed with cornified epithelial cells. C: The smear from a proestrus rat is characterized by a predominance of round nucleated cells of uniform size, with a complete absence of leucocytes. Cells are distributed individually or in clusters. D: Estrus, nonnucleated cornified epithelial cells are predominant.

Figure 2

The uterine tube weight and plasma estrogen concentration are positively correlated. A: the uterine tube weight from rats in proestrus (n=12) is significantly greater than rats in metestrus/diestrus (n=12). B: Rats in proestrus (n=6) had significantly greater plasma estrogen concentration than rats in metestrus/diestrus (n=12). C: the uterine tube weight is positively correlated with plasma estrogen level. ^# t-test p<0.001 compared with met/di. * linear regression p<0.05.

Figure 3

Rats in proestrus are more sensitive to colorectal distention compared with rats in metestrus/diestrus (n=12 per group). A: the threshold for eliciting a visceromotor response in proestrus rats is significantly lower than metestrus/diestrus rats. * Rank sum test p<0.05; B: The magnitude of the visceromotor response to graded intensities of distention was significantly greater at each distention pressure in rats in proestrus compared to rats in metestrus/diestrus. * Two way RM ANOVA p<0.05.