Larsson M, Arvidsson S, Ekman C, Bayati A
Department of Integrative Pharmacology, Research Area CV & GI, Preclinical R&D, AstraZeneca, Mölndal, Sweden.
Neurogastroenterol Motil. 2003 Aug;15(4):371-81. doi: 10.1046/j.1365-2982.2003.00418.x.
In the current study, colorectal distension (CRD) was performed in conscious mice, in order to study visceral (colon) sensitivity. Electrodes were chronically implanted into the external oblique muscle to obtain the electromyographic (EMG) response to CRD. CRD was performed using a computerized system, which inflated the balloon with air to the desired pressures. An increasing (10-80 mmHg) and a repeated (12 x 55 mmHg) phasic paradigm with distensions lasting 10 s and with 5-min intervals were used. The EMG recordings were linearly correlated to intracolonic pressures between 10 and 80 mmHg, which are characteristic of the visceromotor response (VMR). Repeated phasic distensions at 55 mmHg resulted in a stable VMR in female mice, but an increasing VMR in male mice. Interestingly, the duration of the VMR was about 5 s, which is shorter than the actual duration of the distension. U-69593 and fentanyl (selective kappa and mu opioid receptor agonists) significantly reduced the VMR at subcutaneous doses of 0.5 and 0.05 mg x kg-1, respectively. In conclusion, a CRD model for repetitive quantitative studies of colorectal sensitivity and evaluation of pharmacological modulation of visceral sensitivity in conscious mice is presented.
在本研究中,对清醒小鼠进行结直肠扩张(CRD),以研究内脏(结肠)敏感性。将电极长期植入腹外斜肌,以获取对CRD的肌电图(EMG)反应。CRD使用计算机系统进行,该系统用空气将气球充至所需压力。采用递增(10 - 80 mmHg)和重复(12×55 mmHg)的阶段性模式,扩张持续10秒,间隔5分钟。EMG记录与10至80 mmHg的结肠内压力呈线性相关,这是内脏运动反应(VMR)的特征。在55 mmHg下重复进行阶段性扩张,雌性小鼠的VMR稳定,而雄性小鼠的VMR增加。有趣的是,VMR的持续时间约为5秒,短于实际扩张持续时间。U - 69593和芬太尼(选择性κ和μ阿片受体激动剂)分别以0.5和0.05 mg·kg-1的皮下剂量显著降低了VMR。总之,本文提出了一种用于清醒小鼠结直肠敏感性重复定量研究及内脏敏感性药理调节评估的CRD模型。