Effect of Estrogen on Bladder Nociception in Rats

Abstract

Purpose We assessed the effect of ovariectomy and estrogen replacement on nociceptive responses to bladder distention in a rat model. Materials and Methods Female Sprague-Dawley rats (Harlan™) underwent ovariectomy or sham surgery. Visceromotor responses (abdominal contractions) to bladder distention were determined 3 to 4 weeks later under isoflurane anesthesia. In rat subsets estrogen was chronically replaced with a subcutaneous estrogen pellet vs a placebo pellet or acutely replaced by subcutaneous injection 24 hours before testing. Effects of estrogen withdrawal were examined in another group of rats by implanting a pellet and explanting the pellet 24 hours before testing. Uterine weight was measured to assess the estrogen dose. Results Visceromotor responses to bladder distention were significantly less vigorous in ovariectomized rats vs controls. Acute estrogen replacement increased visceromotor responses in these rats but chronic estrogen replacement did not. Sudden chronic estrogen withdrawal resulted in increased visceromotor responses. Uterine weight was consistent with the physiological estrogen dose. Conclusions Estrogen alone was not sufficient to produce increased nociceptive responses but an acute decrease in estrogen resulted in increased visceromotor responses. These data suggest that the pronociceptive effects of estrogen may be due to a mismatch between peripheral vs central and/or genomic vs nongenomic effects of the hormone, which occur during rapidly decreasing estrogen levels.

A Clinically Relevant Animal Model of Temporomandibular Disorder and Irritable Bowel Syndrome Comorbidity

“…Estrogen is pronociceptive in many visceral pain models in rodents. Ovariectomy decreased the magnitude of the visceromotor response to colonic or bladder distention which was restored by bolus estradiol replacement 31,32,53 . An important observation from the current study is consistent with fluctuating plasma E2 concentration as a necessary component for the chronic hypersensitivity.…”

“…Likewise, currently available animal models of pain arising from the viscera or the temporomandibular joint fluctuate across the estrous cycle and are sensitive to hormonal manipulation 3,9,18,31,33,37,41,47,53 . Estrogen is pronociceptive in many visceral pain models in rodents.…”

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS)

“…Immunohistochemical data obtained on specimens of trigonal bladder mucosa did not show a different pattern of estrogen and progesterone receptors in women with and without IC/BPS [24]. However, the vulva and the bladder share a common innervation pathways due to the same embryologic origin [25] and basic research has shown that estrogens modulate nerve density and types of nerve fibers [26,27]. Moreover, a potential modulatory role of estrogens on pain threshold, neurogenic inflammation and immune responses is highly conceivable throughout genomic and non-genomic actions [28,29].…”

“…Individual domain scores (desire, arousal, lubrication, orgasm, satisfaction, and pain) and full-scale score (ranging from 2 to 36) were calculated. A cutoff score 26.55 has been identified to diagnose FSD [18,19].…”

Challenges in experimental stroke research : The 17β-estradiol example

“…Uterine weight is a frequently used bioassay for estrogenic effects [141,144,151,152] and this outcome was used in Paper I to assess the value of such an approach and investigate the correlation with serum 17β-estradiol concentrations. Immediately after sacrifi ce, the uteri were removed through an abdominal midline incision and weighed.…”