Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve

Abstract

Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies have suggested that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included sham ovariectomy (sham OVX), ovariectomy (OVX), OVX with estradiol replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed using repeated cystometrograms (CMGs) to measure micturition thresholds (MT) before and hourly for 3 h after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX group. As expected, bladder inflammation induced bladder hyperreflexia in sham OVX rats (studied in estrus). This hyperreflexia was eliminated by OVX and restored by either estradiol replacement or HYPX. Combining estradiol replacement and HYPX (i.e., OVX+E+HYPX) did not increase the severity of bladder hyperreflexia compared with either manipulation alone. These results indicate that the bladder hyperreflexia that is induced by bladder inflammation requires the presence of estradiol and suggest that this hormonal modulation is exerted via the sympathetic control of the bladder, possibly via an increase of beta-adrenergic inhibitory actions on the detrusor muscle. Similar mechanisms may contribute to bladder disorders in postmenopausal women.

Comparison of the effects of complete and incomplete spinal cord injury on lower urinary tract function as evaluated in unanesthetized rats

“…One could speculate that varying hormonal levels during the estrus cycle could influence the re-emergence of phasic EUS activity after SCI in females, as has been reported for female rats in a bladder inflammation model, with rats in proestrus and estrus exhibiting more severe bladder hyperreflexia than rats in metestrus and diestrus (Johnson and Berkley 2002;Dmitrieva and Berkley 2005). In addition, both estrogen and progesterone have been shown to be neuroprotective after spinal cord trauma.…”

Opposing viscerovisceral effects of surgically induced endometriosis and a control abdominal surgery on the rat bladder

“…Before discussing these two effects, it is important to point out that recent studies have shown that the effects of inflammation on the bladder are influenced by the rat's reproductive status (31,32). Thus, even though estrous stage was controlled in the present study (i.e., all rats were studied in proestrus when E 2 levels are high; Freeman [33]), it is possible that the effects observed here differ in other reproductive conditions.…”

Characterization of bladder sensory neurons in the context of myelination, receptors for pain modulators, and acute responses to bladder inflammation

“…Numerous studies have implicated estrogens in pain modulation e.g., (Robbins et al, 1990, 1992; Sanoja and Cervero, 2005; Gintzler and Liu, 2012), including direct attenuation of TRPV1 responses to capsaicin (Xu et al, 2008). In particular, hormonal status influences bladder activity, as well as the development and severity of a number of pelvic visceral pain conditions including interstitial cystitis (Shea et al, 2000; Johnson and Berkley, 2002; Robinson and Cardozo, 2003; Dmitrieva and Berkley, 2005; Warren et al, 2011). Understanding the precise targets of estrogens in bladder sensory pathways is critical to understanding their function and potentially targeting this mechanism to modulate pain.…”