Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Neuroscience. 2010 Feb 3;165(3):675-83. doi: 10.1016/j.neuroscience.2009.08.076. Epub 2009 Sep 16.
The prefrontal cortex plays a key role in the perception of painful stimuli, including those emerging from the viscera. Colorectal distension is a non-invasive stimulus used to study visceral pain processing in the nervous system. Visceral hypersensitivity is one of the main characteristics of the functional bowel disorder irritable bowel syndrome (IBS). Moreover, recent human neuroimaging studies have emphasized the importance of altered brain activity and circuitry in the manifestation of IBS symptom severity and reaction to visceral stimuli. It is unclear whether animal models of visceral hypersensitivity display a similar response. Therefore, in the present study, we have used c-Fos protein immunoreactivity as an indicator of cell activation, to compare the response of the viscerally hypersensitive Wistar-Kyoto (WKY) rat and control Sprague-Dawley (SD) rat strains to colorectal distension (CRD), a noxious visceral stimulus. Several corticolimbic structures were analysed including the prelimbic cortex, infralimbic cortex and the rostral and caudal anterior cingulate cortices. Moreover, visceral hypersensitivity was also assessed behaviourally in both strains. As previously described WKY rats had a lower pain threshold than SD controls in response to CRD. In all brain regions analysed, exposure to CRD induced an increase in c-Fos activation in both the WKY and SD rats. However, an exaggerated cell activation was found in the prelimbic, infralimbic and rostral anterior cingulate cortices of the WKY rat compared to SD animals. No significant difference was found in caudal anterior cingulate cortex activation when the strains were compared. These results demonstrate, to our knowledge, for the first time an augmented colorectal distension-induced prefrontal cortex activity in WKY rats similar to that seen in IBS patients, further supporting the use of this strain as a model in which to study brain-gut axis dysregulation observed in IBS.
前额皮质在疼痛刺激的感知中发挥着关键作用，包括来自内脏的刺激。结肠扩张是一种非侵入性刺激，用于研究神经系统中的内脏疼痛处理。内脏高敏性是功能性肠病肠易激综合征 (IBS) 的主要特征之一。此外，最近的人类神经影像学研究强调了大脑活动和回路改变在 IBS 症状严重程度和对内脏刺激反应中的重要性。目前尚不清楚内脏高敏性的动物模型是否表现出类似的反应。因此，在本研究中，我们使用 c-Fos 蛋白免疫反应作为细胞激活的指标，比较了内脏高敏性 Wistar-Kyoto (WKY) 大鼠和对照 Sprague-Dawley (SD) 大鼠对结肠扩张 (CRD) 的反应，CRD 是一种有害的内脏刺激。分析了几个皮质边缘结构，包括额前皮质、下额前皮质以及前扣带皮质的额部和尾部。此外，还在这两种品系中评估了内脏高敏性的行为。如前所述，与 SD 对照相比，WKY 大鼠对 CRD 的反应具有较低的疼痛阈值。在分析的所有脑区中，CRD 暴露均导致 WKY 和 SD 大鼠的 c-Fos 激活增加。然而，与 SD 动物相比，WKY 大鼠的额前皮质、下额前皮质和前扣带皮质的细胞激活明显增强。当比较两种品系时，在前扣带皮质尾部没有发现激活的显著差异。这些结果首次证明，与 IBS 患者相似，WKY 大鼠的结肠扩张诱导的前额皮质活动增强，进一步支持使用这种品系作为研究 IBS 中观察到的脑-肠轴失调的模型。
