The 5-HT3 Receptor-Dependent Facilitatory Influence of the Infralimbic Cortex on the Caudal Ventrolateral Medulla Visceral Pain-Related Neurons and Its Colitis-Associated Changes in Rats

The medial prefrontal cortex has been shown to participatein pain processing and to undergo structural and functional changesin chronic visceral pain syndromes. Its infralimbic region (IL)is directly involved in central autonomic regulation and providesextensive projections to pain-related brain centers, being mostcapable of modulating visceral nociception. However, the preciseneuronal and molecular mechanisms underlying IL-exerted descendingcontrol of visceral pain and their probable alterations in pathologyremain unknown. Considering the high levels of serotonin 5-HT3 receptorsin the IL and their important role in visceral pain regulation,in this study performed in anesthetized adult male Wistar rats,we aimed to determine whether 5-HT3 receptor-dependent mechanismsare involved in the IL influence on visceral pain-responsive neuronsof the caudal ventrolateral medulla (CVLM) and whether intestinalinflammation affects the process. Our results showed that electricalstimulation of the IL caused a facilitation of both excitatory andinhibitory CVLM neuron responses to noxious colorectal distension(CRD). Both effects were 5-HT3-dependent, being decreased following intracerebroventricularinjection of a 5-HT3-antagonist, granisetron (20 µg in 10 µL saline).In trinitrobenzenesulfonic acid-induced colitis, the IL stimulatinginfluence on CRD-excited CVLM neurons intensified, while the cortex-drivenfacilitation of CRD-inhibited cells reduced; both appeared resistantto the 5-HT3 receptor blockade. These data provide an insight tothe specific mechanisms underlying cortical modulation of acuteand gut pathology-associated visceral nociception, promoting thedevelopment of differentiated strategies for their treatment.