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The strong gender bias of IC/BPS and limited reports of symptom variations with menstrual status suggest hormonal involvement. Pseudorabies virus (PRV) induced murine neurogenic cystitis recapitulates key aspects of IC/BPS, including altered bladder permeability, trafficking of mast cells to the lamina propria and pelvic specific pain. Rudick and colleagues from Chicago examined the role of reproductive hormones in PRV-induced pelvic pain by comparing the effects of gender, hormonal manipulation, and genetic background in a murine neurogenic cystitis model.
One model of IC/BPS pathogenesis involves a positive feedback loop with substance P containing peripheral nerves stimulating mast cells, which in turn release inflammatory mediators that induce urothelial inflammation and feedback on sensory nerves. IC/BPS has a propensity to occur in females with symptoms that worsen premenopausally or during ovulation and are thought to improve during the hormonal changes of pregnancy in some cases. Estrogen receptor a and B are found in the bladder, and estrogen receptor B-deficient female mice show IC/BPS pathology, suggesting a mechanistic link between estrogen receptor function and cystitis.
The Northwestern University research group demonstrated that female mice showed significantly greater pelvic pain responses after PRV infection than males of 2 genetic backgrounds, suggesting that the gender difference in murine pelvic pain is a general phenomenon consistent with the IC/BPS gender bias. Loss of barrier function of the urothelium was slightly greater in female than in male mice. Data suggested that gender differences observed are not the major determinant of gender differences in pelvic pain. Overall inflammation was not significantly higher in intact female mice than in mice with ovariectomy, but there was no significant difference between male and female mice. The authors conclude that pathophysiology does not mediate gender specific pelvic pain.
Pain responses were not significantly altered by ovariectomy or by acute estrogen replacement in mice with ovariectomy. This finding tends to undermine the hypothesis that reproductive hormones are the key determinant of gender based pelvic pain in neurogenic cystitis.
This article is detailed and requires a close read. The authors conclude that this model of murine neurogenic cystitis shows a gender bias in pelvic pain that does not correlate with bladder pathophysiology. Pelvic pain is not influenced by ovarian hormone status, but genetic background influences pelvic pain severity.
Rudick CN, Pavlov VI, Chen MC, Klumpp DJ
J Urol. 2012 Feb;187(2):715-24
http://dx.doi.org/10.1016/j.juro.2011.10.048
PubMed Abstract
PMID: 22177208
