NEURAL CIRCUITRY MEDIATING SUCROSE INDUCED ANALGESIA

University Of Tennessee Health Sci Ctr, Memphis TN

Investigators

Linked publications & trials

Abstract

DESCRIPTION (adapted from the applicant's 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. Taste buds responsive to sweet-tasting 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 pathways to the parabrachial (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 periaqeductal grey (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 substrates underlying the antinociceptive effect of oral sucrose. A coordinate set of Fos mapping, tract tracing and lesion studies will be used to pinpoint the sites(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.