Phenotypic distinctions between the nodose and jugular TRPV1-positive vagal sensory neurons in the cynomolgus monkey

Abstract

Vagal capsaicin-sensitive afferent C-fibers play an important role in the maintenance of visceral homeostasis and contribute to symptoms in visceral diseases. Based on their developmental origin two functionally distinct types of vagal C-fibers are recognized: those with neurons in the vagal nodose ganglia (derived from epibranchial placodes) and in the vagal jugular ganglia (from neural crest). Studies in nonprimate species demonstrated that the vagal nodose and jugular C-fibers differ in activation profile, neurotrophic regulation, and expression of neurotransmitters. We hypothesized that the expression of selected markers related to key phenotypic properties of vagal C-fibers in the cynomolgus monkey is similar to that reported in nonprimate species. We performed single-cell RT-PCR on nodose and jugular putative C-fiber (TRPV1-positive) neurons isolated from the cynomolgus monkey. We found that the expression of purinergic P2X receptors that underlie selective responsiveness of nodose C-fiber terminals to ATP was conserved in that P2X2 and P2X3 subunits were expressed in nodose, but only P2X3 subunit was expressed in jugular TRPV1-positive neurons. Also conserved was the preferential expression of neurotrophic receptor TrkB in the nodose and preprotachykinin-A in the jugular TRPV1-positive neurons. Several key distinctions in gene expression between nodose and jugular TRPV1-positive (C-fiber) neurons that have been noted in mice, rats, and guinea pigs, are conserved in the cynomolgus monkey. Our results support the translatability of distinct vagal C-fiber phenotypes to primates.

Figure 1.

Vagal jugular and nodose afferent ganglia and adjacent structures (right side) in the cynomolgus monkey.

Figure 2.

The expression of mRNA of selected phenotypic markers detected by single cell RT-PCR in nodose and jugular TRPV1-positive neurons in the cynomolgus monkey. Representative gels. Individual neurons are numbered. +, positive control, -, negative control.