The mechanism of bladder overactivity associated with spinal cord injury : Involvement of plasticity of bladder afferent nerves and nerve growth factors

(1)从Th 8-Th 9细胞水平研究大鼠脊髓横断后膀胱功能的变化。在切断后1周进行膀胱测压时，大鼠未显示反射性膀胱收缩。而膀胱反射性收缩则出现于切断后2周，收缩幅度增加至切断后4周。(2)雌性Sprague-Dawley大鼠，正常或脊髓横断在Th 8-Th 9的水平，膀胱测压研究等容条件下之前和之后膀胱内施用辣椒素或树脂毒素。脊髓横断导致膀胱重量显著增加。在对照和CSI动物中，膀胱内盐水滴注诱导可被六甲双铵阻断的可再现的RBC。横断后4周，CSI动物的阈值体积显著大于对照组，即使在校正膀胱重量后也是如此。平均振幅和d ...更多信息 两组之间RBC的形成没有差异，但CSI动物中的频率显著较低。辣椒素（0.1和1 mM）和树脂毒素（1和10 μ M），膀胱内滴注，发现抑制红细胞在正常和CSI大鼠。两组之间对药物的反应没有质的差异。然而，树脂毒素的效力比辣椒素强约100倍。辣椒素和resiniferatoxin抑制红细胞在正常和CSI大鼠，这表明在感觉纤维（C和Adelta），这是敏感的这些药物的作用，是由膀胱充盈在两种类型的大鼠的活动。(see J. Urol，161：314-319，1999）。(3)鞘内注射选择性神经激肽（NK）_1受体拮抗剂RP 67580，对正常和脊髓损伤大鼠的红细胞有剂量依赖性的抑制作用。RP 67580的抑制作用在对照组和SCI大鼠之间没有显著差异。而选择性NK_2受体拮抗剂MEN 10376鞘内给药对两种大鼠的红细胞均无影响。(4)对6例慢性脊柱病变患者进行膀胱灌注辣椒素治疗逼尿肌过度活动性尿失禁的临床和尿动力学观察。所有6例患者均对治疗有反应，治疗后1个月无尿失禁。这些结果提示辣椒素敏感性初级传入神经的可塑性可能参与脊髓损伤后逼尿肌过度活动的病理生理过程。NGF的可能参与将被调查。少

(1) Functional changes of the bladder after spinal transection at the level of Th8-Th9 in rats were investigated. When examine cystometrically 1 week after the transection, the rats showed no reflexic bladder contractions. However, reflexic bladder contractions emerged at two weeks after the transection, the amplitude of the contractions increased until 4 weeks after the transection.(2) Female Sprague-Dawley rats, normal or with spinal transection at the level of Th8-Th9, were investigated cystometrically under isovolumetric conditions before and after intravesical administration of capsaicin or resiniferatoxin. Spinal transection induced a significant increase in bladder weight. In both control and CSI animals, intravesical saline instillation induced reproducible RBCs that could be blocked by hexamethonium. Four weeks after the transection, the CSI animals had a significantly larger threshold volume than the controls, even after correction for bladder weight. The mean amplitude and d … More uration of the RBCs did not differ between the two groups, but the frequency was significantly lower in CSI animals. Both capsaicin (0.1 and 1 mM) and resiniferatoxin (1 and 10 muM), instilled intravesically, were found to inhibit RBCs in both normal and CSI rats. There were no qualitative differences in the response to the drugs between the two groups. However, resiniferatoxin was approximately 100 times more potent than capsaicin. Capsaicin and resiniferatoxin inhibited RBCs in both normal and CSI rats, suggesting that activity in sensory fibers (C and Adelta), which are sensitive to the action of these drugs, is initiated by bladder filling in both types of rat. (see J.Urol., 161 : 314-319, 1999).(3) Intrathecal administration of RP67580, a selective Neurokinin (NK)_1 receptor antagonist, dose-dependently inhibited RBCs in both control and SCI rats. There was no significant difference regarding the inhibitory effect of RP67580 between the controls and SCI rats. On the other hand, MEN10376, a selective NK_2 receptor antagonist, administered intrathecally, had no effects on RBCs in either type of rats.(4) The clinical and urodynamic effects of intravesical instillation of capsaicin on urinary incontinence due to detrusor overactivity were investigated in 6 patients with chronic spinal lesions. All the six patients responded to the treatment and showed no urinary incontinence at 1 month after treatment. The effect lasted for at least 3 months after treatment.These results suggest that neuroplasticity of the capsaicin-sensitive primary afferents may be involved it the pathophysiology of the detrusor overactivity associated with spinal cord injury. The possible involvement of NGF will be investigated. Less