The effect of tramadol on sneeze-induced urethral continence reflex through μ-opioid receptors in the spinal cord in rats
The effect of tramadol on sneeze-induced urethral continence reflex through μ-opioid receptors in the spinal cord in rats
复制标题
曲马多通过脊髓μ阿片受体对打喷嚏引起的尿道失禁反射的影响
DOI：
10.1002/nau.23518
复制
发表时间：
2018
影响因子：
2
通讯作者：
Saito Seiichi
中科院分区：
文献类型：
--
作者：
Ashikari Asuka;Miyazato Minoru;Kimura Ryu;Oshiro Takuma;Saito Seiichi
目的我们检查了曲马多对大鼠打喷嚏时尿道反射的功效，以及脊髓中 μ-阿片受体的作用。方法使用 41 只雌性 Sprague-Dawley 大鼠。这些大鼠被分为正常雌性大鼠和阴道扩张（VD）大鼠，模拟人类压力性尿失禁（SUI）。在乌拉坦麻醉下，在两组大鼠中使用带有微换能器尖端的导管静脉注射曲马多后检查喷嚏引起的尿道反应幅度（AUR）和基线压力（BP）。在正常大鼠中检查静脉注射曲马多后鞘内注射赛普罗迪（一种选择性 µ-阿片受体拮抗剂）的效果。还对两组静脉注射曲马多后的倾斜漏点压力(tilt LPP)进行了评估。结果在正常大鼠中，曲马多使AUR和BP分别增加33.2%和19.5%。曲马多还使患有 VD 的大鼠血压升高 13.9%，但并没有改变 AUR。单独鞘内注射赛普罗迪不会改变 AUR，但会降低血压。然而，曲马多引起的 AUR 增加被鞘内注射 cyprodime 所阻断，而血压则恢复至给予 cyprodime 之前的水平。曲马多与倾斜 LPP 显着升高相关：在正常大鼠和 VD 大鼠中分别为 24.8% 和 19.5%。结论这些研究结果表明曲马多可有效增强脊髓水平的 AUR 和外周血压。因此，刺激脊髓μ-阿片受体可能有助于治疗 SUI。
AimsWe examined the efficacy of tramadol on the urethral reflex during sneezing, as well as the role of µ‐opioid receptors in the spinal cord, in rats.MethodsForty‐one female Sprague‐Dawley rats were used. The rats were divided into normal female rats and rats with vaginal distension (VD), which mimics stress urinary incontinence (SUI) in humans. Under urethane anesthesia, the sneeze‐induced amplitude of urethral responses (AUR) and baseline pressure (BP) were examined after intravenous injection of tramadol using a microtransducer‐tipped catheter in both rat groups. The effect of intrathecal cyprodime, a selective µ‐opioid receptor antagonist, following intravenous tramadol injection was examined in normal rats. The tilt leak point pressure (tilt LPP) after intravenous tramadol injection was also evaluated in both groups.ResultsIn normal rats, tramadol enhanced the AUR and BP by 33.2% and 19.5%, respectively. Tramadol also increased BP by 13.9% in rats with VD, but it did not change AUR. Intrathecal cyprodime alone did not change AUR, but it decreased BP. However, tramadol‐provoked increments in AUR were blocked by intrathecal cyprodime, while BP was recovered to the level that it was before administration of cyprodime. Tramadol was associated with a significant elevation in tilt LPP: 24.8% and 19.5% in normal and VD rats, respectively.ConclusionsThese findings suggest that tramadol effectively enhances the AUR at the spinal level and BP peripherally. Therefore, stimulation of the spinal µ‐opioid receptors may be useful for the treatment of SUI.