Han Jin-Hee, Kim Sung-Eun, Ko Il-Gyu, Kim Jayoung, Kim Khae Hawn
Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, Seoul, Korea.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Int Neurourol J. 2017 Sep;21(3):178-188. doi: 10.5213/inj.1734984.492. Epub 2017 Sep 12.
The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB).
In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated.
SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB.
Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.
下尿路（LUT）的功能，如排尿和储尿，依赖于位于大脑、脊髓和外周神经节的复杂中枢神经网络。因此，LUT的功能易受包括脊髓损伤（SCI）在内的各种神经系统疾病影响。颈段或胸段脊髓损伤会破坏排尿的自主控制以及协调膀胱和括约肌功能的正常反射通路。在这种情况下，值得注意的是，据报道α1肾上腺素能受体阻滞剂可缓解良性前列腺增生（BPH）老年男性的排尿症状和储尿症状。坦索罗辛，一种α1肾上腺素能受体阻滞剂，也被认为是治疗LUT症状如BPH和膀胱过度活动症（OAB）患者的最有效方案。
在本研究中，研究了坦索罗辛对SCI大鼠传入排尿区域，包括脑桥排尿中枢（PMC）、腹外侧导水管周围灰质（vlPAG）和脊髓（L5）中c-Fos、神经生长因子（NGF）和烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）表达的影响。
发现SCI显著上调排尿传入通路、L5背角、vlPAG和PMC中c-Fos、NGF和NADPH-d的表达，导致OAB症状。相比之下，坦索罗辛治疗显著抑制了这些神经活动以及排尿传入通路中一氧化氮的产生，因此减轻了OAB症状。
基于这些结果，α1肾上腺素能受体拮抗剂坦索罗辛可用于减轻SCI后的膀胱功能障碍。然而，需要进一步研究以阐明坦索罗辛对排尿传入通路的确切机制和作用。
