Zhang Xiaoyang, Douglas Kristy L, Jin Huixia, Eldaif Bassem M, Nassar Rashid, Fraser Matthew O, Dolber Paul C
Department of Surgery, Veterans Affairs Medical Center, Duke University Medical Center, Durham, NC 27710, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R2084-96. doi: 10.1152/ajpregu.90653.2008. Epub 2008 Oct 22.
The primary afferent neurotransmitter triggering the spinal micturition reflex after complete spinal cord injury (SCI) in the rat is unknown. Substance P detected immunohistochemically in the sacral parasympathetic nucleus was significantly higher in 12 SCI rats than in 12 spinally intact rats (P = 0.008), suggesting substance P as a plausible candidate for the primary afferent neurotransmitter. The effects of the tachykinin NK1 receptor antagonist L-733060 on the spinal micturition reflex were then determined by performing conscious cystometry in an additional 14 intact rats and 14 SCI rats with L-733060 (0.1-100 microg) administered intrathecally at L6-S1. L-733060 was without effect in intact rats, but blocked the spinal micturition reflex in 10 of 14 SCI rats and increased the intermicturition interval in 2 of 4 others at doses ranging from 10 to 100 microg. Both phasic and nonphasic voiding contractions, differentiated according to the presence of phasic external urethral sphincter (EUS) activity, were present in most SCI rats. Both types of contractions were blocked by high doses of L-733060. Interestingly, there was a relative decline in phasic voiding contractions at high doses as well as a decline in contraction amplitude in nonphasic voiding contractions. In other respects, cystometric variables were largely unaffected in either spinally intact or SCI rats. L-733060 did not affect tonic EUS activity at any dose except when the spinal micturition reflex was blocked and tonic activity was consequently lost. These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats.
大鼠脊髓完全损伤（SCI）后触发脊髓排尿反射的初级传入神经递质尚不清楚。免疫组织化学检测发现，12只SCI大鼠骶副交感核中检测到的P物质显著高于12只脊髓完整的大鼠（P = 0.008），提示P物质可能是初级传入神经递质的候选者。然后，通过对另外14只完整大鼠和14只SCI大鼠进行清醒膀胱测压，确定速激肽NK1受体拮抗剂L-733060对脊髓排尿反射的影响，L-733060（0.1 - 100微克）经鞘内注射至L6 - S1。L-733060对完整大鼠无作用，但在14只SCI大鼠中有10只阻断了脊髓排尿反射，在另外4只中的2只中，剂量为10至100微克时增加了排尿间隔时间。大多数SCI大鼠中存在根据相位性尿道外括约肌（EUS）活动区分的相位性和非相位性排尿收缩。两种类型的收缩均被高剂量的L-733060阻断。有趣的是，高剂量时相位性排尿收缩相对下降，非相位性排尿收缩的收缩幅度也下降。在其他方面，膀胱测压变量在脊髓完整或SCI大鼠中基本未受影响。L-733060在任何剂量下均不影响紧张性EUS活动，除非脊髓排尿反射被阻断且紧张性活动因此丧失。这些实验表明，速激肽在脊髓NK1受体上的作用在SCI大鼠的脊髓排尿反射中起主要作用。
