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

Kollarik, Mariana; Ru, Feib; Undem, Bradley J.b

doi: 10.1097/WNR.0000000000001231

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.

aDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida

bDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Correspondence to Marian Kollarik, MD, PhD, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd., MDC-4029, Tampa, FL 33612, USA Tel: +1 813 974 1616; Fax: +1 813 974 3079; e-mail:

Received February 18, 2019

Accepted February 26, 2019

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