Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Apr;127(4):431-444.
doi: 10.1007/s00702-020-02161-7. Epub 2020 Feb 22.

Cross-talk signaling in the trigeminal ganglion: role of neuropeptides and other mediators

Karl Messlinger  1 , Louis K Balcziak  2 , Andrew F Russo  3   4
Affiliations
Review

Cross-talk signaling in the trigeminal ganglion: role of neuropeptides and other mediators

Karl Messlinger et al. J Neural Transm (Vienna). 2020 Apr.

Abstract

The trigeminal ganglion with its three trigeminal nerve tracts consists mainly of clusters of sensory neurons with their peripheral and central processes. Most neurons are surrounded by satellite glial cells and the axons are wrapped by myelinating and non-myelinating Schwann cells. Trigeminal neurons express various neuropeptides, most notably, calcitonin gene-related peptide (CGRP), substance P, and pituitary adenylate cyclase-activating polypeptide (PACAP). Two types of CGRP receptors are expressed in neurons and satellite glia. A variety of other signal molecules like ATP, nitric oxide, cytokines, and neurotrophic factors are released from trigeminal ganglion neurons and signal to neighboring neurons or satellite glial cells, which can signal back to neurons with same or other mediators. This potential cross-talk of signals involves intracellular mechanisms, including gene expression, that can modulate mediators of sensory information, such as neuropeptides, receptors, and neurotrophic factors. From the ganglia cell bodies, which are outside the blood-brain barrier, the mediators are further distributed to peripheral sites and/or to the spinal trigeminal nucleus in the brainstem, where they can affect neural transmission. A major question is how the sensory neurons in the trigeminal ganglion differ from those in the dorsal root ganglion. Despite their functional overlap, there are distinct differences in their ontogeny, gene expression, signaling pathways, and responses to anti-migraine drugs. Consequently, drugs that modulate cross-talk in the trigeminal ganglion can modulate both peripheral and central sensitization, which may potentially be distinct from sensitization mediated in the dorsal root ganglion.

Keywords: CGRP; Dorsal root ganglion; Neuropeptides; Satellite glial cells; Sensory neurons; Signaling; Trigeminal ganglion.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Histology and immunohistochemistry of rat trigeminal ganglion. a Horizontal section (hematoxylin–eosin staining) showing clusters of primary afferent somata (dark violet) in the ophthalmic (V1), maxillary (V2) and mandibular division (V3). b–e are from the V1 region. b, c Neurons showing immunofluorescence for CGRP (red) and neuronal NO synthase (nNOS, green), respectively, in the same section. Of the 4 large, about 10 medium-sized and about 15 small neurons, 3 medium-sized and 7 small neurons are clearly CGRP immunopositive, and 4 neurons are also immunopositive for nNOS. Courtesy of Anne Dieterle, Erlangen. d Double immunostaining for the CGRP receptor components RCP (red) and CLR (green) plus DAPI nucleus staining (blue) indicating functional units. Several neurons show both RCP and CLR immunoreactivity (yellow). e Neurons immunostained for the CGRP receptor components RAMP1 (red). RAMP1 immunoreactive neurons are generally less frequent than CLR and RCP immunoreactive neurons. Courtesy of Mária Dux, Szeged
Fig. 2
Fig. 2
Representation of receptor expression and signaling processes in and between trigeminal ganglion cells. Small neurons (with C-fibers) expressing CGRP may signal to satellite glial cells (SGCs) and to middle-sized neurons (with Aδ or C-fibers) expressing CGRP receptors. CGRP release by Ca2+-dependent exocytosis can be induced by activating Ca2+-conducting ion channels like TRPA1, for example, by nitroxyl (NO−). Autocrine activation by CGRP may occur via CGRP-binding amylin receptors. CGRP and amylin receptors may activate intracellular cascades involving cAMP response-element binding protein (CREB) or mitogen-activated protein kinase (MAPK) to induce gene expression of purinergic (P2X3) receptor channels in neurons and purinergic (P2Y) receptors in SGCs, enzymes like nitric oxide synthase (NOS), cytokines like tumor necrosis factor (TNFα) as well as growth factors like brain-derived neurotrophic factor (BDNF). Nitric oxide (NO), cytokines and BDNF may signal back to neurons facilitating expression of purinergic receptor channels, CGRP and CGRP receptor components like RAMP1. In addition, ATP released from neurons may activate SGCs and macrophage-like cells (MLC), which can signal back to neurons by cytokines. Many of the gene products like CGRP, CGRP receptor proteins and BDNF can crucially influence neuronal transduction and synaptic transmission, because they are delivered by axonal transport through the neuronal processes to the peripheral and/or central terminals of trigeminal afferents
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahn AH, Basbaum AI. Where do triptans act in the treatment of migraine? Pain. 2005;115:1–4. doi: 10.1016/j.pain.2005.03.008. - DOI - PMC - PubMed
    1. Ahn AH, Basbaum AI. Tissue injury regulates serotonin 1D receptor expression: implications for the control of migraine and inflammatory pain. J Neurosci. 2006;26:8332–8338. doi: 10.1523/JNEUROSCI.1989-06.2006. - DOI - PMC - PubMed
    1. Ambalavanar R, Morris R. The distribution of binding by isolectin I-B4 from Griffonia simplicifolia in the trigeminal ganglion and brainstem trigeminal nuclei in the rat. Neuroscience. 1992;47:421–429. doi: 10.1016/0306-4522(92)90256-2. - DOI - PubMed
    1. Ambalavanar R, Moritani M, Dessem D. Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. Pain. 2005;117:280–291. doi: 10.1016/j.pain.2005.06.029. - DOI - PubMed
    1. Anderson LE, Seybold VS. Calcitonin gene-related peptide regulates gene transcription in primary afferent neurons. J Neurochem. 2004;91:1417–1429. doi: 10.1111/j.1471-4159.2004.02833.x. - DOI - PubMed

Publication types