Visceral targets specify calcitonin gene-related peptide and substance P enrichment in trigeminal afferent projections

Abstract

Rat trigeminal ganglion projections to a visceral target (intracranial blood vessels) are enriched in calcitonin gene-related peptide (CGRP) and substance P (Sub P) compared to trigeminal ganglion projections to a cutaneous target (the forehead skin). We asked if transplants of a novel visceral target (fetal stomach antrum tissue) into the path of the neonatal rat trigeminal frontal nerve projection to forehead skin would induce neuronal CGRP and Sub P enrichment. By postnatal day (P) 25, the percentage of nerves containing CGRP increased from 14-15% in the control trigeminal projection to forehead skin to 20-31 % (in different experiments) in the trigeminal projection to transplanted stomach antrum. The percentage of Sub P-containing neurons increased from 10% in the control forehead skin projection to 22% in the trigeminal projection to stomach transplants over the same time period. The number of neurons in the trigeminal frontal nerve projection to stomach antrum transplants was not significantly different from the number of frontal neurons projecting to control forehead skin. We suggest that respecification of trigeminal neurons to the CGRP and Sub P phenotype, not selective survival of CGRP- and Sub P-positive afferents, is the mechanism by which stomach antrum induces enrichment of CGRP and Sub P. A subpopulation of rat trigeminal neurons with cutaneous forehead skin projections also sends a transient axon collateral projection to a visceral target (the cerebral arteries) during early postnatal development. Postnatal maintenance of an axonal projection to a cutaneous target (forehead skin) may be incompatible with a neuron also maintaining a visceral collateral to the cerebral arteries. Neonatal transplants of stomach antrum were made into the path of the trigeminal projection to forehead skin. This tested whether frontal nerve projections to a novel visceral target would protect these individual trigeminal neurons from the normal retraction of their visceral axon collaterals to the cerebral arteries. Fourteen percent of trigeminal neurons in the cutaneous projection to the forehead skin also project to the middle cerebral artery at P5 in control rats. By P90, all of these cells survive and maintain cutaneous forehead skin projections, but almost all have retracted their artery collaterals in control animals. Less than 4% of trigeminal neurons projecting to transplanted stomach antrum retain their cerebral artery col-lateral projection at P25, the same low percentage of cells retaining artery collaterals in the trigeminal projection to control transplants of forehead skin at this age. Thus, in the trigeminal system, postnatal forehead target phenotype is important in regulating neurotransmitter expression in neuronal afferents, but may not be the critical factor controlling the axon collateral distribution of neurons projecting to multiple peripheral targets.