Dataset Information

Effect of transcutaneous cervical vagus nerve stimulation on the pituitary adenylate cyclase-activating polypeptide (PACAP) response to stress: A randomized, sham controlled, double blind pilot study.

ABSTRACT: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that plays a key role in the neurobiology of the stress response, and prior studies suggest that its function is dysregulated in post-traumatic stress disorder (PTSD). Transcutaneous cervical vagus nerve stimulation (tcVNS) acts through PACAP and other neurobiological systems to modulate stress responses and/or symptoms of PTSD. In this pilot study, we examined the effects of tcVNS on PACAP in a three day chronic stress laboratory paradigm involving serial traumatic and mental stress exposures in healthy individuals with a history of exposure to psychological trauma (n = 18) and patients with PTSD (n = 12).

Methods

A total of 30 subjects with a history of exposure to psychological trauma experience were recruited (12 with PTSD diagnosis) for a three-day randomized double-blinded study of tcVNS or sham stimulation. Subjects underwent a protocol that included both personalized trauma recall and non-personalized mental stressors (public speaking, mental arithmetic) paired to tcVNS or sham stimulation over three days. Blood was collected at baseline and multiple time points after exposure to stressors. Linear mixed-effects models were used to assess changes in PACAP over time (in response to stressors) and its relation to active tcVNS or sham stimulation.

Results

PACAP blood levels increased over the course of three days for both active tcVNS and sham groups. This increase was statistically-significant in the sham group at the end of the second (Cohen's d_rm = 0.35, p = 0.04), and third days (d_rm = 0.41, p = 0.04), but not in the active tcVNS group (d_rm = 0.21, d_rm = 0.18, and p > 0.20).

Conclusion

These pilot findings suggest tcVNS may attenuate this neurobiological stress-response. Larger studies are needed to investigate gender and interaction effects.

SUBMITTER: Gurel NZ

PROVIDER: S-EPMC9216713 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-conserved neuropeptide characteristic of vertebrates. This pluripotent hypothalamic neuropeptide regulates neurotransmitter release, intestinal motility, metabolism, cell division/differentiation, and immunity. In vertebrates, PACAP has a specific receptor (PAC1) but it can also activate the Vasoactive Intestinal Peptide receptors (VPAC1 and VPAC2). The evolution of the vertebrate PACAP ligand - receptor pair has been well-described. In contrast, the situation in invertebrates is much less clear. The PACAP ligand - receptor pair in invertebrates has mainly been studied using heterologous antibodies raised against mammalian peptides. A few partial PACAP cDNA clones sharing >87% aa identity with vertebrate PACAP have been isolated from a cnidarian, several protostomes and tunicates but no gene has been reported. Moreover, current evolutionary models of the peptide and receptors using molecular data from phylogenetically distinct invertebrate species (mostly nematodes and arthropods) suggests the PACAP ligand and receptors are exclusive to vertebrate genomes. A basal deuterostome, the cephalochordate amphioxus (Branchiostoma floridae), is the only invertebrate in which elements of a PACAP-like system exists but the peptides and receptor share relatively low sequence conservation with the vertebrate homolog system and are a hybrid with the vertebrate glucagon system. In this study, the evolution of the PACAP system is revisited taking advantage of the burgeoning sequence data (genome and transcriptomes) available for invertebrates to uncover clues about when it first appeared. The results suggest that elements of the PACAP system are absent from protozoans, non-bilaterians, and protostomes and they only emerged after the protostome-deuterostome divergence. PACAP and its receptors appeared in vertebrate genomes and they probably shared a common ancestral origin with the cephalochordate PACAP/GCG-like system which after the genome tetraploidization events that preceded the vertebrate radiation generated the PACAP ligand and receptor pair and also the other members of the Secretin family peptides and their receptors.