Neural circuitry mediating sucrose induced analgesia

• Grant number: 97/11034-9
• Support Opportunities: Scholarships abroad - Research
• Start date: January 15, 1998
• End date: January 14, 2000
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Vanessa Cristina Zilli Anseloni de Sousa
• Grantee: Vanessa Cristina Zilli Anseloni de Sousa
• Host Investigator: Michael Shipley Matthew Ennis
• Host Institution: Pessoa Física
• Institution abroad: University of Maryland, Baltimore (UMB), United States

Abstract

Studies by Blass and colleagues demonstrate profound antinociceptive and calming effects of oral ingestion of sucrose, milk and fat in newborn rats and humans. Sucrose-induced analgesia in rats and humans develops within seconds, lasts for minutes and is prevented by opiate receptor antagonists. Thus, the mechanisms appear to be remarkably well conserved phylogenetically. The neural circuits by which taste stimuli engage central analgesic mechanisms are not known. Caste buds responsive to sweet stimuli are located mostly on the palate in the rat. They project via the superficial petrosal nerve and synapse in discrete target zones in the rostral, gustatory portion of nucleus tractus solitarius (rNTS). Gustatory information then ascends via well defined pathways to the parabrachial complex (PBC), ventrobasal thalamus, central nucleus of the amygdala (CNA) lateral hypothalamic area (LHA) and insular cortex (IC). Although analgesia can be elicited from a constellation of sites ranging from the frontal lobe to the brainstem, there is consensus that two major nodal points are involved in circuitry that produces opiate-mediated analgesia: the midbrain periaqueductal gray (PAG) and nucleus raphe magnus (NRM). Based on the finding that opiate receptor antagonists prevent sucrose-induced analgesia, we hypothesize that sucrose engages opiate analgesia via activation of PAG or NRM descending output neurons. Recent work in our laboratory suggests several potential sites of interaction between gustatory and central analgesia circuits. Ascending gustatory pathways synapse in PBC and ultimately terminate in IC and CNA. We have shown that PBC, IC LHA and CNA send dense projections to PAG. Stimulation of PBC, LHA and CNA elicits analgesia. However, we do not know if gustatory responsive neurons in these areas project to PAG, or if other gustatory nuclei project to PAG or NRM. The goal of this project is to identify the anatomical substrate(s) underlying the antinociceptive effect of oral sucrose. A coordinate set of Fos mapping, tract tracing and lesion studies will be used to pinpoint the site(s) of linkage between gustatory nuclei and descending pain inhibitory circuits and to verify that these links are necessary for the, production of sucrose-induced analgesia. This work will lead to a better understanding of neural circuits controlling taste and pain and how these circuits regulate analgesia in newborns. (AU)