急性骶神经刺激通过脊髓阿片类途径降低大鼠内脏机械敏感性。
Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway.
作者信息
Langlois L, Meleine M, Ouelaa W, Caremel R, Bridoux V, Benard M, Dechelotte P, Ducrotte P, Grise P, Leroi A M, Gourcerol G
机构信息
Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.
Department of Urology, Rouen University Hospital, Rouen, France.
出版信息
Neurogastroenterol Motil. 2015 Jun;27(6):816-23. doi: 10.1111/nmo.12555. Epub 2015 Mar 25.
BACKGROUND
Sacral nerve stimulation (SNS) is an alternative surgical treatment of refractory urge incontinence and/or fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS remain poorly understood. The aim of this experimental study was to evaluate the effect of SNS on visceral mechanosensitivity in rats.
METHODS
Anesthetized Sprague-Dawley rats were treated with SNS or sham stimulation. SNS was performed by implanting an electrode close to the sacral nerve root S1. Rats were administered either a non-selective opioid receptor antagonist (naloxone) or a nitric oxide synthase inhibitor (L-NAME). Colonic mechanosensitivity was evaluated using the variation of arterial blood pressure as a spino-bulbar reflex in response to graded isobaric colorectal distension (CRD). C-fos immunoreactive neurons were quantified in spinal and supraspinal sites. μ-opioid receptor (MOR) internalization was counted in the sacral spinal cord with sham or effective SNS in response to CRD.
KEY RESULTS
SNS reduced visceral mechanosensitivity in response to CRD. This effect was reversed by intrathecal and intraveinous naloxone administration. In both models, CRD induced increased c-fos immunoreactivity in the dorsal horn neurons of the sacral spinal cord and supraspinal areas. This increase was prevented by SNS. MOR internalization was significantly higher in stimulated group.
CONCLUSIONS & INFERENCES: SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.
背景
骶神经刺激(SNS)是治疗难治性急迫性尿失禁和/或大便失禁的一种替代性外科治疗方法。尽管其具有临床疗效,但SNS的作用机制仍知之甚少。本实验研究的目的是评估SNS对大鼠内脏机械敏感性的影响。
方法
对麻醉后的Sprague-Dawley大鼠进行SNS或假刺激治疗。通过将电极植入靠近骶神经根S1处来进行SNS。给大鼠注射非选择性阿片受体拮抗剂(纳洛酮)或一氧化氮合酶抑制剂(L-NAME)。使用动脉血压变化作为脊髓-延髓反射来评估结肠机械敏感性,以响应分级等压结肠扩张(CRD)。对脊髓和脊髓上部位的C-fos免疫反应性神经元进行定量。在假刺激或有效SNS的情况下,对骶脊髓中响应CRD的μ-阿片受体(MOR)内化进行计数。
主要结果
SNS降低了对CRD的内脏机械敏感性。鞘内和静脉内注射纳洛酮可逆转这种作用。在两种模型中,CRD均诱导骶脊髓背角神经元和脊髓上区域中C-fos免疫反应性增加。SNS可防止这种增加。刺激组的MOR内化明显更高。
结论与推论
SNS通过降低对CRD的脊髓-延髓反射来影响内脏机械敏感性。脊髓阿片受体可能参与了这种作用。