Colorectal distension-induced prefrontal cortex activation in the Wistar-Kyoto rat: implications for irritable bowel syndrome

Abstract

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.