Motawie Ayat A, Abd Al-Aziz Amany M, Hamed Hanan M, Fatouh Amany A A, Awad Mona A M, El-Ghany Amany Abd
Pediatric Department, National Research Centre, Cairo, Egypt.
Pediatric Department, National Research Centre, Cairo, Egypt.
J Pediatr Urol. 2017 Feb;13(1):46.e1-46.e5. doi: 10.1016/j.jpurol.2016.08.030. Epub 2016 Oct 24.
Primary nocturnal enuresis is one of the sleep related phenomena characterized by disruption in the relationship between arousal and urination. Corticotropin-releasing factor (CRF) is a neurohormone released from the paraventricular nucleus of the hypothalamus into the median eminence to elicit release of adrenocorticotrophin from the anterior pituitary. It may act to modulate autonomic function and behavior in concert with the endocrine effects. Conflicting animal studies about the role of CRF in micturition, either facilitating or inhibiting, have been raised. It was suggested to be a novel target for treatment of urinary disorders based on the finding that manipulation of CRF in the pontine micturition circuit could affect urodynamic function.
The aim was to throw light on the possible role of CRF in primary monosymptomatic nocturnal enuresis by assessing its serum level.
Twenty-nine children aged 8-14 years complaining of primary monosymptomatic nocturnal enuresis and 16 age- and sex-matched healthy children with good toilet control day and night were recruited to the study. History taking, clinical examination, and assessment of serum CRF levels in the morning and evening (9 a.m. and 9 p.m.) were carried out for all patients and controls.
A positive family history of enuresis was detected in 82.8% of enuretic patients. Serum levels of CRF (both morning and evening) were significantly lower in patients than in controls. Several animal studies suggested that CRF in descending projections from Barrington's nucleus to the lumbosacral parasympathetic neurons is inhibitory to micturition, which supports our results and the assumption that reduction of the evening serum CRF level could have a role in the occurrence of primary monosymptomatic nocturnal enuresis. No significant difference was found between morning and evening CRF serum levels in either cases or controls, which negates our assumption of having a rhythmic pattern of release (figure). No correlations with age were found. According to their history, all our enuretic patients were deep sleepers. Deep sleep and difficult arousal were found to have a major role in primary monosymptomatic nocturnal enuresis. It was proposed that CRF function may allow arousal to occur before micturition to facilitate preparative behaviors. A lower CRF level may explain deep-sleep pattern in children with enuresis.
CRF was deficient in our enuretic children, which may draw attention to the possible pathophysiological implications in primary nocturnal enuresis (either at the level of loss of inhibitory effect on micturition or lack of arousal in response to bladder distension). Further proof studies are recommended.
原发性夜间遗尿症是一种与睡眠相关的现象,其特征是觉醒与排尿之间的关系受到干扰。促肾上腺皮质激素释放因子(CRF)是一种从下丘脑室旁核释放到正中隆起的神经激素,可促使垂体前叶释放促肾上腺皮质激素。它可能与内分泌效应协同作用,调节自主神经功能和行为。关于CRF在排尿中作用的动物研究结果相互矛盾,既有促进排尿的作用,也有抑制排尿的作用。基于在脑桥排尿回路中对CRF进行调控可影响尿动力学功能这一发现,有人提出CRF是治疗泌尿系统疾病的一个新靶点。
通过评估血清水平来阐明CRF在原发性单纯性夜间遗尿症中可能发挥的作用。
招募了29名年龄在8至14岁、主诉原发性单纯性夜间遗尿症的儿童,以及16名年龄和性别匹配、昼夜排尿控制良好的健康儿童作为研究对象。对所有患者和对照组进行病史采集、临床检查,并分别于上午9点和晚上9点测定血清CRF水平。
82.8%的遗尿症患者有遗尿症家族史阳性。患者的血清CRF水平(上午和晚上)均显著低于对照组。多项动物研究表明,从巴林顿核向下投射至腰骶部副交感神经元的CRF对排尿有抑制作用,这支持了我们的研究结果以及以下假设:夜间血清CRF水平降低可能与原发性单纯性夜间遗尿症的发生有关。无论是患者还是对照组,上午和晚上的CRF血清水平均无显著差异,这否定了我们关于其有节律性释放模式的假设(图)。未发现与年龄相关的相关性。根据病史,我们所有的遗尿症患者均为深度睡眠者。发现深度睡眠和难以觉醒在原发性单纯性夜间遗尿症中起主要作用。有人提出,CRF的功能可能是使觉醒在排尿前发生,以促进准备行为。较低的CRF水平可能解释遗尿症儿童的深度睡眠模式。
我们的遗尿症儿童存在CRF缺乏的情况,这可能使人们关注原发性夜间遗尿症可能的病理生理学意义(无论是在对排尿抑制作用丧失的层面,还是在对膀胱扩张缺乏觉醒反应的层面)。建议进行进一步的验证研究。