Endometriosis-induced vaginal hyperalgesia in the rat: Effect of estropause, ovariectomy, and estradiol replacement

• Type of Material: Article
• Authors: Karen J. Berkley, Florida State University; Stacy McAllister, Emory University; Briane E. Accius, Florida State University; Kenneth P. Winnard, Florida State University
• Language: English
• Date: 2007-11
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: (C) 2007 Lippincott Williams & Wilkins, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pain.2007.09.022
• Title of Journal or Parent Work: PAIN
• ISSN: 0304-3959
• Volume: 132
• Start Page: S150
• End Page: S159
• Grant/Funding Information: This study was supported by NIH grant RO1-NS11892.
• Keywords: pelvic pain; estrous cycle; viscero-visceral effects; aging; vulvodynia
• Research Categories: Biology, Neuroscience; Health Sciences, Obstetrics and Gynecology

Abstract

Endometriosis (ENDO) is a painful disorder defined by extrauteral endometrial growths. It is created in rats by autotransplanting pieces of uterus (which form cysts), or, for shamENDO, fat (no cysts). ENDO induces vaginal hyperalgesia, likely via central sensitization. The severity of this hyperalgesia correlates with estradiol levels during the estrous cycle, suggesting the hyperalgesia is estradiol-modulated. If so, then hyperalgesic severity should track estradiol changes during reproductive senescence (estropause) when estradiol levels initially decrease, then increase. Using psychophysical methods to assess vaginal nociception, we found that the severity of ENDO-induced hyperalgesia paralleled estradiol changes during estropause: hyperalgesia first decreased, then returned. Furthermore, the return occurred regardless of the presence of the cysts (excised in some rats). This finding provides further support for ENDO’s likely centrally-mediated effects. Additionally, the results suggest that elimination of estradiol via ovariectomy (OVX) should alleviate ENDO-induced hyperalgesia and estradiol replacement should restore it. However, in healthy and shamENDO rats, OVX produces a vaginal hyperalgesia that is alleviated by estradiol, likely via estradiol’s peripheral influences on the vagina. Hence, we tested the hypothesis that OVX in ENDO rats would trigger a different type of vaginal hyperalgesia dependent on the loss of estradiol. We predicted that the opposing influences of estradiol on ENDO- and OVX-induced hyperalgesia would cancel each other. As predicted, OVX had no effect on ENDO-induced hyperalgesia and estradiol replacement alleviated it. These results suggest that, in intact rats, ENDO-induced vaginal hyperalgesia is exacerbated by estradiol, and that different mechanisms underlie ENDO-induced versus OVX-induced vaginal hyperalgesia.