| Co-Investigator(Kenkyū-buntansha) |
SEKI Satoshi Shinshu Univ.Hospital, Dept.of Urology Assistant Professor, 医学部・附属病院, 助手 (60293502)
MIZUSAWA Hiroya Shinshu Univ.Hospital, Dept.of Urology Assistant Professor, 医学部・附属病院, 助手 (50293535)
ISHIZUKA Osamu Shinshu Univ.Hospital, Dept.of Urology Assistant Professor, 医学部・附属病院, 講師 (20184541)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
(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
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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
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