探討源於橋腦背外側四疊體之下行路徑對脊髓上骨盆神經─尿道反射塑性的調控

Investigation on descending modulation from dorsolateral potine tegmentum on spinal pelvic nerve-to-urethral sphincter reflex plasticity

彭賢祐(Hsien-Yu Peng)

指導教授 ： 陳進典 ； 林則彬

中山醫學大學/醫學院/醫學研究所/碩士(2005年)

https://doi.org/10.6834/CSMU.2005.00084

摘要

本篇實驗為研究電刺激和化學刺激大白鼠的橋腦背外側四疊體 (dorsolateral pontine tegmentum；簡稱DLPT)，達到調控骨盆神經─尿道反射上 (pelvic nerve-to-urethra sphincter reflex簡稱；PUR) 神經塑性的效果，並且探討該反應與血清胺接受器 (serotonin receptor) 之間的相關性。實驗過程中比較單獨刺激骨盆神經 (pelvic nerve) 與同時刺激骨盆神經與橋腦背外側四疊體，記錄外尿道括約肌的肌動作電位 (External urethral sphincter electromyogram；簡稱EUSE) 變化情形。首先以30秒為間隔予以刺激，此種刺激模式稱作測試性刺激 (test stimulation, 1/30 Hz；簡稱TS)，此時的動作電位數為 (1.00±0.00 spikes/stimulation)，接著對骨盆傳入神經給予每秒一次的刺激，稱之為反覆性刺激 (repetitive stimulation, 1 Hz；簡稱RS) ，此時動作電位數為 (16.12±1.59 spikes/stimulation)，該反覆性電刺激所引起的反應可以被NBQS削減 (7.42±0.57 spikes/stimulation)；投予APV 則幾乎完全阻斷 (1.57±0.29 spikes/stimulation)。另一方面，對橋腦背外側四疊體與骨盆神經，同步施予電刺激時 (synchronized train pontine stimulation on pelvic afferent nerve repetitive stimulation；簡稱PS+RS)，可促進反覆性刺激骨盆神經引發的反射增益效應 (25.17±2.21 spikes/stimulation)，這說明，此種刺激模式會對原先由RS引發的增益效應 (16.12±1.59 spikes/stimulation) 產生促進的調控效應；此種促進現象可以被椎管內注射血清胺1A型接受器之拮抗劑 (5HT-1A receptor antagonist) WAY-100653所阻斷 (14.66±1.58 spikes/stimulation)；另一方面，若於反覆性刺激，產生骨盆─尿道反射增益效應時，以椎管注射方式給予血清胺1A型接受器之致效劑 (5HT-1A receptor agonist) 8-OH-DPAT，則可以獲得 (RS+DPAT, 26.16±1.05 spikes/stimulation) 類似同時刺激骨盆神經和橋腦背外側四疊體的數據。依實驗結果發現，刺激橋腦背外側四疊體後，可經橋腦脊髓下行路徑，引發骨盆─尿道反射中的塑性增益作用，而且血清胺可能參與其中。然而，此一透過下行路徑調控反射塑性的作用，也許與生理或病理狀態下儲尿機轉有關。
延續上述實驗，將橋腦背外側四疊體的刺激模式由電刺激改為化學刺激，在RS (16.14±0.96 spikes/stimulation) 引發反射增益效應的情境下，於高位中樞 (higher center) 橋腦背外側四疊體分別給予：乙醯膽鹼 (acetylcoline；簡稱ACh) 、蕈毒鹼 (muscarine；簡稱M)、尼古丁 (nicotine；簡稱N)，結果發現乙醯膽鹼 (RS+ACh, 23.57±2.23 spikes/stimulation) 和尼古丁 (RS+N, 28.29±2.36 spikes/stimulation) 的參與皆可以顯著的促進反覆性刺激骨盆神經引發的反射增益效應有顯著的促進效果；在投予蕈毒鹼 (RS+M, 18.14±2.19 spikes/stimulation) 的實驗組中，則不會產生促進的現象。接著，在RS+N組中，以椎管內注射的方式給予WAY-100653 (RS+N+WAY, 12.86±3.13 spikes/stimulation) 可將尼古丁產生的促進效應阻斷。上述結果顯示，尼古丁或尼古丁型接受器可能與橋腦背外側四疊體調控骨盆尿道反射的增益效應有關。

關鍵字

脊髓 ； 反射 ； 橋腦背外側四疊體 ； 血清胺 ； 增益

並列摘要

The aim of the current study is to investigate whether or not the stimulation-induced plasticity in pelvic nerve-to-urethra sphincter reflex (PUR) activities can be modulated by a dorsolateral pontine tegmentum (DLPT) stimulation and whether or not the serotoninergic mechanism is involved in this modulation. The external urethral sphincter electromyogram (EUSE) responses to the pelvic afferent nerve test stimulation (TS, 1/30 Hz) or repetitive stimulation (RS, 1 Hz) in 30 anesthetized rats were recorded with/without synchronized train pontine stimulation or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (NBQX, 100 uM), D-2-amino-5-phosphonoraleric acid (APV, 100 uM), N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) injections. Pelvic afferent nerve TS evoked a single EUSE action potential (1.00±0.00 spikes/stimulation), whereas RS produced a long-lasting EUSE potentiation (16.12±1.59 spikes/stimulation). This RS-induced reflex plasticity was abolished by APV (1.57±0.29 spikes/stimulation) and attenuated by NBQX (7.42±0.57 spikes/stimulation). Superimpose of synchronized train pontine stimulation on pelvic afferent nerve repetitive stimulation (PS+RS) produced facilitation in RS-induced plasticity (25.17±2.21 spikes/stimulation). The facilitaion in reflex plasticity resulted from synchronized pontine stimulation was abolished WAY-100653 (14.66±1.58 spikes/stimulation). On the other hand, intrathecal 8-OH-DPAT elicited facilitaion on the RS-induced plasticity (26.16±1.05 spikes/stimulation) without pontine stimulation. ACh (RS+ACh, 23.57±2.23 spikes/stimulation) or nicotine (RS+N, 28.29±2.36 spikes/stimulation) injection into the DLPT facilitated PUR plasticity but physiological saline or muscarine (RS+M, 18.14±2.19 spikes/stimulation) elicited no effect. This Nicotine-induced facilitation on PUR plasticity was abolishd by i.t. injection of WAY-100683 (RS+N+WAY, 12.86±3.13 spikes/stimulation). Our findings suggest that dorsolateral pontine tegmentum did modulate pelvic nerve-to-urethral sphincter reflex plasticity via serotoninergic neurotransmission. This descending modulation maybe physiological/pathological relevance in urine continence.

並列關鍵字

spinal cord ； reflex ； pontine tegmentum ； serotonin ； potentiation

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