Arvidsson Susanne, Larsson Marie, Larsson Håkan, Lindström Erik, Martinez Vincente
Integrative Pharmacology-Gastrointestinal Biology, AstraZeneca R&D Mölndal, Mölndal, Sweden.
J Pain. 2006 Feb;7(2):108-18. doi: 10.1016/j.jpain.2005.09.003.
Recently, a new manometric method has been proposed to quantify visceromotor responses (VMR) to colorectal distension (CRD) in rats. This method is based on monitoring pressure changes within the distending balloon during CRD. This study assesses the applicability of such a technique to the quantification of VMRs to CRD in mice. Electrical activity of the abdominal muscles and pressure changes within the distending balloon (mechanical response) were simultaneously recorded in conscious mice during CRD (phasic ascending, 10-80 mm Hg, or repetitive, 55 mm Hg). There was a clear stimulus-response relationship with a strong correlation between electrical and mechanical responses during the ascending (r(2) = 0.899, n = 7) or repetitive phasic CRD (r(2) = 0.926, n = 8). Repetitive phasic distensions (55 mm Hg) increased the mechanical and electrical responses by 71 +/- 20% and 42 +/- 16%, respectively (pulses 10-12 vs. 1-3; n = 8, both P < .01). Atropine (0.5 or 1 mg/kg, subcutaneously) did not affect the mechanical response to CRD. The mu-opioid agonist, fentanyl (0.05 mg/kg, subcutaneously), completely prevented the sensitizing response associated to repetitive distensions. These results show that noninvasive, surgery-free manometry of intracolonic pressure is a reliable method to assess VMRs to CRD in mice. The analgesic effect of compounds could be determined, indicating that the method can be used in pharmacologic studies.
The model presented to assess visceral pain in mice allows a broad use of this species in pharmacological studies and will be of use in the characterization of potential targets and new drugs for the treatment of human pathologies with visceral pain arising from the gut as a significant component.
最近，有人提出了一种新的测压方法来量化大鼠对结直肠扩张（CRD）的内脏运动反应（VMR）。该方法基于在CRD期间监测扩张球囊内的压力变化。本研究评估了这种技术在量化小鼠对CRD的VMR方面的适用性。在清醒小鼠进行CRD（阶段性上升，10 - 80 mmHg，或重复性，55 mmHg）期间，同时记录腹部肌肉的电活动和扩张球囊内的压力变化（机械反应）。在上升阶段（r² = 0.899，n = 7）或重复性阶段性CRD（r² = 0.926，n = 8）期间，电活动和机械反应之间存在明显的刺激 - 反应关系且相关性很强。重复性阶段性扩张（55 mmHg）使机械反应和电活动反应分别增加了71±20%和42±16%（第10 - 12次脉冲与第1 - 3次脉冲相比；n = 8，P均 < 0.01）。阿托品（0.5或1 mg/kg，皮下注射）不影响对CRD的机械反应。μ阿片类激动剂芬太尼（0.05 mg/kg，皮下注射）完全阻止了与重复性扩张相关的敏化反应。这些结果表明，结肠内压力的无创、无需手术的测压法是评估小鼠对CRD的VMR的可靠方法。可以确定化合物的镇痛作用，表明该方法可用于药理学研究。
所提出的评估小鼠内脏痛的模型使得该物种在药理学研究中得到广泛应用，并将有助于表征潜在靶点以及用于治疗以肠道内脏痛为重要组成部分的人类疾病的新药。
