Search

Abstract: Estrogen reportedly facilitates visceral nociception at the spinal or supraspinal level. The present study was aimed to investigate whether estrogen modulates visceral pain through the vagal pathway. Ovariectomized rats received estradiol, which was administered subcutaneously (to act through both the vagal and spinal pathways) or intraduodenally (to preferentially act through the vagal pathway). Luminally applied estradiol induced a rapid and significant decrease in the visceromotor response to colorectal distension, with increased c-Fos expression in nodose ganglion neurons. Systemically injected estradiol increased visceromotor response and c-Fos expression in both nodose and dorsal root ganglion (T6-12) neurons. The antinociceptive effect of estrogen was abolished by surgical vagotomy or chemical denervation of vagal afferents. Both luminally and systemically administered estradiol elicited selective 5-hydroxytryptamine secretion from the duodenum. Granisetron, a 5-hydroxytryptamine 3 receptor antagonist, reversed the antinociceptive effect of estrogen. Intestinal mucosal mast cell stabilizers prevented estradiol-induced antinociception and 5-hydroxytryptamine secretion. Ultrastructural analysis revealed that estradiol caused piecemeal degranulation of intestinal mucosal mast cells. The actions of estradiol were inhibited by an estrogen receptor β antagonist and mimicked by an estrogen receptor β agonist. These results suggest that estrogen can trigger vagus-mediated antinociception, which is masked by its spinally mediated pronociception. Perspective: This study is the first to show a vagus-mediated estrogenic antinociception, in which the nongenomic estrogen receptor β–mediated, intestinal mucosal mast cell–derived 5-hydroxytryptamine/5-hydroxytryptamine 3 receptor pathway is involved. This work may provide new insights into the sex hormone modulation of visceral sensitivity related to irritable bowel syndrome and indicate potential therapeutic targets to manage this disease. [Copyright &y& Elsevier]

Objective Chordoid meningioma (CM) and clear-cell meningioma (CCM) are rare World Health Organization grade II meningioma subtypes. This study aimed to evaluate favorable factors and appropriate therapeutic strategies for these lesions. Methods We retrospectively reviewed clinical data from 111 cases of grade II meningiomas, including 55 cases of CM and 56 cases of CCM, between January 2011 and December 2015. Results The mean follow-up time of the rare World Health Organization grade II meningiomas ( n = 111) was 45.3 months. In the CM group, 8 patients (14.5%) experienced recurrence, and 2 patients (3.6%) died. In the CCM group, 22 patients (39.3%) experienced recurrence, and 9 patients (16.1%) died. Significant differences were observed between the CM and CCM groups in tumor size ( P = 0.019), history of surgery ( P = 0.038), and peritumoral edema ( P = 0.004). In the CM group, gross total resection was associated with favorable progression-free survival (hazard ratio, 0.144; 95% confidence interval, 0.029–0.714; P = 0.018). In the CCM group, univariate analyses showed that preoperative Karnofsky Performance Status <80 ( P < 0.001), tumor size ≥5 cm ( P = 0.015), tumor size (per-centimeter increase) ( P = 0.022), bone invasion ( P = 0.004), a history of surgery ( P < 0.001), and subtotal resection ( P = 0.009) were associated with worse progression-free survival. Male gender ( P = 0.039), tumor size (per-centimeter increase) ( P = 0.043), bone invasion ( P = 0.030), and a history of surgery ( P = 0.007) were associated with poor overall survival. Conclusions This study showed that gross total resection should be achieved in grade II meningiomas. Patients with larger tumors and/or surgical histories had worse outcomes. [ABSTRACT FROM AUTHOR]