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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-4 (01))
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Davis, Barry
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Anseloni, V C Z; Ren, K; Dubner, R et al. (2005) A brainstem substrate for analgesia elicited by intraoral sucrose. Neuroscience 133:231-43
Anseloni, V; Ren, K; Dubner, R et al. (2004) Ontogeny of analgesia elicited by non-nutritive suckling in acute and persistent neonatal rat pain models. Pain 109:507-13
Anseloni, Vanessa C Z; Ennis, Matthew; Lidow, Michael S (2003) Optimization of the mechanical nociceptive threshold testing with the Randall-Selitto assay. J Neurosci Methods 131:93-7
Anseloni, Vanessa C Z; Weng, H-R; Terayama, R et al. (2002) Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models. Pain 97:93-103