Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Eur Urol. 2012 Dec;62(6):1157-64. doi: 10.1016/j.eururo.2012.03.031. Epub 2012 Mar 23.
Botulinum neurotoxin A (BoNTA), which alleviates overactive bladder symptoms, is thought to act predominantly via the inhibition of transmitter release from parasympathetic nerves. However, actions at other sites such as afferent nerve terminals are possible.
To evaluate the effects of BoNTA on bladder afferent neuropeptide release and firing.
DESIGN, SETTING, AND PARTICIPANTS: One side of the bladder of control and chronic (1-2 wk) spinal cord transected (SCT; T(8)-T(9)) adult female mice was injected with BoNTA (0.5 U/5 μl saline). After 48 h, bladders with L(6)-S(2) spinal nerves were prepared for in vitro recordings.
In bladder preparations, tension and optical mapping of Ca(2+) transients were used to measure intrinsic contractions, those evoked by capsaicin or the electrical stimulation of spinal nerves. Afferent firing was evoked by stretch or intrinsic bladder contractions. The numbers of responding units and firing rates were measured. Animal numbers were used to detect moderate to large between-group differences based on Cohen's criteria. Two-way analysis of variance was used to test spatial/temporal differences in Ca(2+) signals as mean plus or minus standard deviation. Differences between data sets were tested with the student t test and skewed data sets with a Mann-Whitney U test (significant when p<0.05).
In control and SCT bladders, BoNTA treatment decreased the contractions evoked by electrical stimulation of spinal nerves without altering intrinsic contractions. Afferent firing on untreated sides in response to stretch/intrinsic contractions was increased in SCTs versus controls. On BoNTA-treated sides, afferent firing rates were greatly attenuated in response to mechanical stimulation as were the capsaicin-evoked optical signals mediated by neuropeptide release.
SCT caused an increased sensitivity of afferent nerves to mechanical stimulation that was reduced by BoNTA treatment. Increased intrinsic activity after SCT was unaffected by the toxin. Thus BoNTA suppresses neurogenic detrusor overactivity by targeting afferent as well as efferent pathways in the bladder.
肉毒杆菌神经毒素 A（BoNTA）可缓解膀胱过度活动症症状，被认为主要通过抑制副交感神经递质的释放来发挥作用。然而，它在其他部位（如传入神经末梢）也可能发挥作用。
评估 BoNTA 对膀胱传入神经肽释放和放电的影响。
设计、地点和参与者：在对照组和慢性（1-2 周）脊髓横断（SCT；T(8)-T(9)）成年雌性小鼠的一侧膀胱中注射 BoNTA（0.5 U/5 μl 生理盐水）。48 h 后，准备带有 L(6)-S(2)脊神经的膀胱进行体外记录。
在膀胱标本中，张力和钙瞬变的光学映射用于测量内在收缩，以及用辣椒素或脊髓神经电刺激诱发的收缩。传入放电是通过伸展或内在膀胱收缩来诱发的。测量反应单位的数量和放电率。根据 Cohen 的标准，使用动物数量来检测组间中度至大的差异。使用双向方差分析来测试 Ca(2+)信号的时空差异，以平均值加或减标准偏差表示。使用学生 t 检验测试数据集之间的差异，使用曼-惠特尼 U 检验测试偏态数据集（当 p<0.05 时为显著差异）。
在对照组和 SCT 膀胱中，BoNTA 处理减少了脊髓神经电刺激诱发的收缩，而不改变内在收缩。与对照组相比，SCT 中未处理侧的传入放电对伸展/内在收缩的反应增加。在 BoNTA 处理的侧，传入放电率在机械刺激下大大减弱，辣椒素诱发的神经肽释放介导的光学信号也减弱。
SCT 导致传入神经对机械刺激的敏感性增加，BoNTA 处理可降低这种敏感性。SCT 后内在活动增加不受毒素影响。因此，BoNTA 通过靶向膀胱中的传出和传入途径抑制神经源性逼尿肌过度活动。
