Mitra Reinika, Aronsson Patrik, Winder Michael, Tobin Gunnar, Bergquist Filip, Carlsson Thomas
J Parkinsons Dis. 2015;5(2):301-11. doi: 10.3233/JPD-140509.
Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson's disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration.
In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson's disease with that of normal untreated animals.
The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an vitro organ bath setup.
Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20-40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10 -4 M concentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5×10 -3 M) during atropine treatment.
Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson's disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson's disease that has previously not been described.
泌尿系统问题，包括尿频、尿急和夜尿症，是帕金森病中与生活质量差相关性最高的一些非运动症状。然而，这些症状背后的机制尚不清楚，尤其是多巴胺变性后的外周膀胱病理生理学。
在本研究中，我们比较了帕金森病6-OHDA单侧大鼠模型的膀胱收缩反应性与正常未处理动物的膀胱收缩反应性。
在体外器官浴装置中，使用电场刺激、毒蕈碱和嘌呤受体刺激，在膀胱条制备物中评估逼尿肌的收缩性。
我们的数据表明，与对照动物相比，6-OHDA损伤大鼠在电场刺激后的总体收缩反应显著更高（在20-40赫兹刺激下最大收缩时为43%）。这种增加与胆碱能收缩反应的显著增加相关，其中毒蕈碱激动剂乙酰甲胆碱在6-OHDA处理的大鼠中产生的反应比对照组高44%（在10-4M浓度下），剂量反应曲线显著左移。这表明在特定的中枢6-OHDA诱导的多巴胺耗竭后，毒蕈碱受体系统的敏感性发生了改变。此外，在阿托品治疗期间，使用激动剂ATP（5×10-3M）激活嘌呤受体时，6-OHDA动物的条带收缩也比对照组大36%。
我们的数据表明，帕金森病中不仅排尿反射的中枢多巴胺控制发生了改变，膀胱的局部收缩功能也发生了改变。本研究提请注意帕金森病中一种以前未被描述的泌尿功能障碍机制。
