Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Neurourol Urodyn. 2018 Jun;37(5):1605-1611. doi: 10.1002/nau.23518. Epub 2018 Feb 10.
We 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.
Forty-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.
In 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.
These 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.
我们研究了曲马多在打喷嚏时对尿道反射的疗效，以及脊髓中μ-阿片受体在大鼠中的作用。
使用 41 只雌性 Sprague-Dawley 大鼠。将大鼠分为正常雌性大鼠和阴道扩张（VD）大鼠，后者模拟人类压力性尿失禁（SUI）。在尿嘧啶麻醉下，通过微传感器导管在两组大鼠中静脉注射曲马多后，检查打喷嚏引起的尿道反应幅度（AUR）和基础压（BP）。在正常大鼠中，检查静脉注射曲马多后鞘内给予环丙胺，一种选择性μ-阿片受体拮抗剂的效果。还评估了两组大鼠静脉注射曲马多后的倾斜漏点压（tilt LPP）。
在正常大鼠中，曲马多分别使 AUR 和 BP 增强 33.2%和 19.5%。曲马多还使 VD 大鼠的 BP 增加了 13.9%，但没有改变 AUR。鞘内环丙胺单独使用不会改变 AUR，但会降低 BP。然而，鞘内环丙胺可阻断曲马多引起的 AUR 增加，而 BP 恢复到给予环丙胺之前的水平。曲马多与倾斜 LPP 的显著升高相关：正常和 VD 大鼠分别为 24.8%和 19.5%。
这些发现表明，曲马多可有效增强脊髓水平的 AUR 和外周 BP。因此，刺激脊髓μ-阿片受体可能对治疗 SUI 有用。
