Estrous changes in vaginal nociception in a rat model of endometriosis
Abstract
A rat model of endometriosis, in which pieces of uterine horn (versus fat in controls) are autotransplanted into the abdomen where they form cysts, reduces fecundity and produces vaginal hyperalgesia. The cysts gradually enlarge over a 2-month period postsurgically and then plateau. Cysts regress with low estrogen levels and reappear when they rise. Based on the hypothesis that the vaginal hyperalgesia depends upon the cysts, this study tested two predictions: that (1) the hyperalgesia would develop postsurgically in parallel with the cysts, and (2) the hyperalgesia would vary with estrous, being greatest when estrogen levels are high (proestrus) and least when low (estrus). In rats trained to escape vaginal distention, percentage escape responses to different distention volumes were measured across the rat's 4-day estrous cycle for 2.5 months before and up to 4 months after autotransplantation of uterus (n=9) or fat (n=6) in abdominal sites. Vaginal pressures were also measured. In rats with uterine but not fat autotransplants, escape percentages increased postsurgically over a 2-month period and then plateaued. The increase was greatest in proestrus and failed to occur in estrus. Vaginal pressures were unchanged in all groups. These results strongly support the hypothesis that the vaginal hyperalgesia depends upon the cysts. Because the cysts were located in sites remote from the vagina, the hyperalgesia involves viscero-visceral interactions and is likely centrally mediated, whereas the estrous modulation could involve hormonal actions either on the cysts or, more likely, on vaginal afferent fibers, and/or on central neurons.
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ENDO rats develop vaginal hyperalgesia accompanied by increased abdominal muscle activity.
“ENDO rats develop vaginal hyperalgesia (Cason et al., 2003), which is accompanied by increased abdominal muscle activity (Nagabukuro and Berkley, 2007b).”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Cason et al., 2003
After cysts stabilize (>8 weeks post-transplant), vaginal nociception varies with estrous stage, with hyperalgesia present in proestrus but absent the next day in estrus.
“Thus, it was found that, after the cysts have stabilized (i.e., more than 8 weeks post-transplant), vaginal nociception varies with estrous stage, with hyperalgesia present in proestrus but absent the next day in estrus [7].”
From Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis (2012) · cites this paper as [7]
ENDO rats exhibit vaginal hyperalgesia.
“ENDO rats exhibit vaginal hyperalgesia.”
From Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis (2012) · cites this paper as [7]
Rats in metestrus, like those in proestrus, evidence vaginal hyperalgesia; the biggest difference in severity of hyperalgesia is between proestrus and estrus.
“because rats in metestrus, like those in proestrus, evidence vaginal hyperalgesia; i.e., the biggest difference in severity of hyperalgesia is between proestrus and estrus [7].”
From Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis (2012) · cites this paper as [7]
Studies were done when the rat was in proestrus, the estrous stage when hyperalgesia in the ENDO model is most severe.
“Studies were done when the rat was in proestrus, the estrous stage when hyperalgesia in the ENDO model is most severe [10,45,38].”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [10]
All assessments were done >6 wks after surgery, when ENDO-induced hyperalgesia is fully-developed and stable.
“All assessments were done > 6 wks after the surgery; i.e., when ENDO-induced hyperalgesia is fully-developed and stable [10,45,38].”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [10]
The ENDO model's surgical control (shamENDO) develops neither cysts nor pain symptoms.
“The ENDO model’s surgical control (shamENDO) develops neither cysts nor pain symptoms [10,38].”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [10]
A rat model of surgically-induced endometriosis (ENDO) develops pain symptoms similar to those of women, including vaginal hyperalgesia and vaginally-referred abdominal muscle hyperalgesia.
“A rat model of surgically-induced endometriosis (ENDO), in which ectopic uterine cysts form in the abdomen [51], develops pain symptoms similar to those of women, including vaginal hyperalgesia (10) and vaginally-referred abdominal muscle hyperalgesia [38].”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [10]
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Self-citation
- Authors
- Cason, A. M., Samuelsen, C. L., & Berkley, K. J.
- Affiliations
- Florida State University (US)
- Corresponding author
- Berkley, Karen J
- ORCID
- Samuelsen, Chad L
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 44
- Issue
- 2
- Pages
- 123-131
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W2004169894
- Cited by
- 94
- References
- 36
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 5
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (1R01 NS 11892, R01NS011892)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- endometriosis, estrous cycle, estrogen, visceral nociception, endometriotic cysts, vaginal distention, escape behavior, vaginal pressure, central pain modulation
- MeSH terms
- Adipose Tissue, Analysis of Variance, Animals, Cysts, Disease Models, Animal, Dyspareunia, Endometriosis, Escape Reaction, Estrogens, Female, Hyperalgesia, Pain Measurement, Uterus, Vagina, Rats, Sprague-Dawley, Estrous Cycle, Rats
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