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Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system

Edvinsson, Jacob Carl Alexander LU ; Grell, Anne Sofie LU ; Warfvinge, Karin LU orcid ; Sheykhzade, Majid ; Edvinsson, Lars LU and Haanes, Kristian Agmund (2020) In Cephalalgia 40(12). p.1296-1309
Abstract

Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of... (More)

Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CGRP, hemi-skull model, PAC1 receptor, PACAP, Sensory nervous system, trigeminal ganglion
in
Cephalalgia
volume
40
issue
12
pages
14 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85086019921
  • pmid:32486909
ISSN
0333-1024
DOI
10.1177/0333102420929026
language
English
LU publication?
yes
id
895def9a-e910-4bde-890c-3fb94cf373ee
date added to LUP
2020-07-03 11:19:23
date last changed
2024-06-13 19:17:00
@article{895def9a-e910-4bde-890c-3fb94cf373ee,
  abstract     = {{<p>Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K<sup>+</sup> or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC<sub>1</sub> was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.</p>}},
  author       = {{Edvinsson, Jacob Carl Alexander and Grell, Anne Sofie and Warfvinge, Karin and Sheykhzade, Majid and Edvinsson, Lars and Haanes, Kristian Agmund}},
  issn         = {{0333-1024}},
  keywords     = {{CGRP; hemi-skull model; PAC1 receptor; PACAP; Sensory nervous system; trigeminal ganglion}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{12}},
  pages        = {{1296--1309}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cephalalgia}},
  title        = {{Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system}},
  url          = {{http://dx.doi.org/10.1177/0333102420929026}},
  doi          = {{10.1177/0333102420929026}},
  volume       = {{40}},
  year         = {{2020}},
}