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

Abstract

The medial prefrontal cortex has been shown to participate in pain processing and to undergo structural and functional changes in chronic visceral pain syndromes. Its infralimbic region (IL) is directly involved in central autonomic regulation and provides extensive projections to pain-related brain centers, being most capable of modulating visceral nociception. However, the precise neuronal and molecular mechanisms underlying IL-exerted descending control of visceral pain and their probable alterations in pathology remain unknown. Considering the high levels of serotonin 5-HT3 receptors in 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 mechanisms are involved in the IL influence on visceral pain-responsive neurons of the caudal ventrolateral medulla (CVLM) and whether intestinal inflammation affects the process. Our results showed that electrical stimulation of the IL caused a facilitation of both excitatory and inhibitory CVLM neuron responses to noxious colorectal distension (CRD). Both effects were 5-HT3-dependent, being decreased following intracerebroventricular injection of a 5-HT3-antagonist, granisetron (20 µg in 10 µL saline). In trinitrobenzenesulfonic acid-induced colitis, the IL stimulating influence on CRD-excited CVLM neurons intensified, while the cortex-driven facilitation of CRD-inhibited cells reduced; both appeared resistant to the 5-HT3 receptor blockade. These data provide an insight to the specific mechanisms underlying cortical modulation of acute and gut pathology-associated visceral nociception, promoting the development of differentiated strategies for their treatment.