Department of Biomedicine, Experimental Biology Unit, Faculty of Medicine of Porto, University of Porto, Porto, Portugal.
Translational NeuroUrology, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.
Neurourol Urodyn. 2019 Aug;38(6):1540-1550. doi: 10.1002/nau.24032. Epub 2019 Jun 10.
To investigate if intravesical administration during spinal shock of resiniferatoxin (RTX), an ultrapotent desensitizing agonist of transient receptor potential vanilloid-1 (TRPV1), would silence TRPV1-expressing bladder afferents at an early stage of disease progression and modulate neurogenic detrusor overactivity (NDO) emergence.
Rats submitted to largely incomplete spinal cord transection at T8/9 spinal segment were treated with intravesical RTX (50 nM) or its vehicle during spinal shock. Four weeks after spinal lesion, bladder-reflex activity was evaluated by cystometry under urethane anesthesia, after which the bladder, spinal cord, and dorsal root ganglia were collected and processed.
We found improvements on bladder function several weeks after early intravesical RTX administration, including a marked decrease of intravesical pressures and amplitude of bladder contractions. Such strong long-lasting urodynamic effects resulted from the very potent desensitizing activity of RTX on peripheral terminals of sensory afferents, an effect restricted to the bladder.
Our results support that an early intervention with RTX could potentially attenuate NDO development and ensuing urinary incontinence, with a dramatic impact on the quality of life of spinal cord injury patients.
研究在脊髓休克期间向膀胱内给予树脂毒素（RTX）——瞬时受体电位香草素 1（TRPV1）的超高效脱敏激动剂——是否会在疾病进展的早期沉默 TRPV1 表达的膀胱传入神经，并调节神经原性逼尿肌过度活动（NDO）的发生。
将大鼠 T8/9 脊髓节段进行不完全性脊髓横断，在脊髓休克期间用膀胱内 RTX（50nM）或其载体进行治疗。脊髓损伤后 4 周，在乌拉坦麻醉下通过膀胱测压法评估膀胱反射活动，然后收集膀胱、脊髓和背根神经节并进行处理。
我们发现早期膀胱内 RTX 给药后数周内膀胱功能得到改善，包括膀胱内压力和膀胱收缩幅度的显著降低。这种强烈的长期尿动力学效应是由于 RTX 对感觉传入神经末梢的超强脱敏作用所致，这种作用仅限于膀胱。
我们的结果支持早期干预 RTX 可能会减弱 NDO 的发展和随之发生的尿失禁，从而对脊髓损伤患者的生活质量产生巨大影响。
