Nijsen M J M A, Ongenae N G H, Coulie B, Meulemans A L
Department of Gastrointestinal and Emerging Diseases, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Pain. 2003 Sep;105(1-2):115-23. doi: 10.1016/s0304-3959(03)00170-2.
Several research groups have measured the visceromotor response to visceral distension by electromyography (EMG) in the conscious restraint, wrapped or lightly anaesthetized rat. Our aim was to develop a more physiological and stress-free technique that enables the simultaneous measurement of duodenal distension-induced visceromotor and cardiovascular responses in the conscious, freely moving rat. A telemetry transmitter, consisting of a bipolar electrode pair and arterial catheter, was chronically implanted into the rat to measure abdominal EMG, mean arterial pressure (MAP) and heart rate (HR). Furthermore, a balloon catheter was chronically implanted in the duodenum to deliver volume-fixed staircase (0.1-0.6 ml) or phasic (0.1, 0.3, 0.5 ml) distensions. The area under the curve (AUC; mVs) and maximal amplitude (EMG(max); mV) during distension were analyzed. The model was validated by pre-treatment with morphine (0.3, 1.5 and 3 mg/kg, intraperitoneally). Staircase and phasic distension produced a volume-dependent increase in AUC and EMG(max), HR and MAP. Pre-treatment with morphine inhibited the distension-induced visceromotor response, i.e. abdominal contractions, increase in AUC and EMG(max). These findings indicate that telemetry is an adequate tool to measure visceromotor and cardiovascular responses to averse, noxious duodenal distension continuously and simultaneously in the rats home cage, without additional handling-related or restraint-induced stress. The presented animal visceral model is intended for studying acute and chronic analgesic properties of new pharmaceutical compounds.
几个研究小组已通过肌电图（EMG）测量了清醒受限、包裹或轻度麻醉大鼠对内脏扩张的内脏运动反应。我们的目的是开发一种更符合生理且无应激的技术，该技术能够在清醒、自由活动的大鼠中同时测量十二指肠扩张诱导的内脏运动和心血管反应。将一个由双极电极对和动脉导管组成的遥测发射器长期植入大鼠体内，以测量腹部肌电图、平均动脉压（MAP）和心率（HR）。此外，将一个球囊导管长期植入十二指肠，以进行体积固定的阶梯式（0.1 - 0.6 ml）或相位式（0.1、0.3、0.5 ml）扩张。分析扩张期间的曲线下面积（AUC；mVs）和最大振幅（EMG(max)；mV）。通过用吗啡（0.3、1.5和3 mg/kg，腹腔内注射）进行预处理来验证该模型。阶梯式和相位式扩张使AUC、EMG(max)、HR和MAP产生了与体积相关的增加。用吗啡预处理可抑制扩张诱导的内脏运动反应，即腹部收缩、AUC和EMG(max)增加。这些发现表明，遥测是一种合适的工具，可在大鼠的饲养笼中连续且同时测量对有害十二指肠扩张的内脏运动和心血管反应，而无需额外的与处理相关或受限诱导的应激。所呈现的动物内脏模型旨在研究新药物化合物的急性和慢性镇痛特性。
