TY - JOUR

T1 - Neuropeptides and the Nodes of Ranvier in Cranial Headaches

AU - Edvinsson, Jacob C. A.

AU - Haanes, Kristian A.

AU - Edvinsson, Lars

N1 - Funding Information: KH was supported by a Lundbeck Foundation Fellowship (R345-2020-1977). Publisher Copyright: Copyright © 2022 Edvinsson, Haanes and Edvinsson.

PY - 2022

Y1 - 2022

N2 - The trigeminovascular system (TGV) comprise of the trigeminal ganglion with neurons and satellite glial cells, with sensory unmyelinated C-fibers and myelinated Aδ-fibers picking up information from different parts of the head and sending signals to the brainstem and the central nervous system. In this review we discuss aspects of signaling at the distal parts of the sensory fibers, the extrasynaptic signaling between C-fibers and Aδ-fibers, and the contact between the trigeminal fibers at the nerve root entry zone where they transit into the CNS. We also address the possible role of the neuropeptides calcitonin gene-related peptide (CGRP), the neurokinin family and pituitary adenylyl cyclase-activating polypeptide 38 (PACAP-38), all found in the TGV system together with their respective receptors. Elucidation of the expression and localization of neuropeptides and their receptors in the TGV system may provide novel ways to understand their roles in migraine pathophysiology and suggest novel ways for treatment of migraine patients.

AB - The trigeminovascular system (TGV) comprise of the trigeminal ganglion with neurons and satellite glial cells, with sensory unmyelinated C-fibers and myelinated Aδ-fibers picking up information from different parts of the head and sending signals to the brainstem and the central nervous system. In this review we discuss aspects of signaling at the distal parts of the sensory fibers, the extrasynaptic signaling between C-fibers and Aδ-fibers, and the contact between the trigeminal fibers at the nerve root entry zone where they transit into the CNS. We also address the possible role of the neuropeptides calcitonin gene-related peptide (CGRP), the neurokinin family and pituitary adenylyl cyclase-activating polypeptide 38 (PACAP-38), all found in the TGV system together with their respective receptors. Elucidation of the expression and localization of neuropeptides and their receptors in the TGV system may provide novel ways to understand their roles in migraine pathophysiology and suggest novel ways for treatment of migraine patients.

KW - nerve entry zone

KW - nodes of Ranvier

KW - Redlich-Obersteiner zone

KW - Remak bundles

KW - trigeminal ganglion

KW - vascular neuroeffector site

U2 - 10.3389/fphys.2021.820037

DO - 10.3389/fphys.2021.820037

M3 - Review

C2 - 35095575

AN - SCOPUS:85123413864

VL - 12

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

M1 - 820037

ER -