Elsevier

Neuroscience

Volume 154, Issue 4, 17 July 2008, Pages 1562-1567
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2008.04.070Get rights and content

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.

Section snippets

Animals

Intact female Sprague–Dawley rats (200–220 g, 9–10 weeks of age) were used in the present study. Rats were housed two per cage, with free access to food and water and maintained on a 12-h light/dark cycle. All protocols were approved by the University of Maryland Dental School Institutional Animal Care and Use Committee and adhered to the guidelines for experimental pain in animals published by the International Association for the Study of Pain. Care was taken to use the minimum number of

Estrous phase

Three measurements were taken into account to identify rats in different stages of the estrous cycle. Intact female rats (n=29) were primarily classified as in metestrus (n=6), diestrus (n=6), proestrus (n=12) or estrus (n=5) on the day of the visceromotor recording according to the cellular characteristics of their vaginal smears (Fig. 1). All rats had four to five day cycles. The weight of the uterus and plasma estrogen concentration were measured and used as the second and third index for

Discussion

In the present study, we used three measurements to determine the phase of the estrous cycle and observed a fluctuation in the magnitude of the visceromotor response with estrous phase, by showing that rats in proestrus (when high plasma estrogen concentration was present) had significantly lower threshold and higher magnitude of response to CRD as compared with rats in metestrus/diestrus (when plasma estrogen concentration was low), further supporting our previous observation that estrogen

Conclusion

In summary, the existence of a sex difference in the prevalence of human chronic pain syndromes such as IBS suggests gonadal hormones could influence visceral pain perception. The mechanisms underlying the sex difference in the clinical condition remain unclear. Our previous observations that there is a sex difference in behavioral and neuronal response to CRD, along with the findings that ovariectomy decreased and estrogen replacement reversed the response to CRD suggest the model could be

Acknowledgments

This work was supported by R01 NS 37424. Authors would like to thank Sangeeta Pandya for technical assistance.

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