PACAP and its role in primary headaches
(2018) In Journal of Headache and Pain 19(1).- Abstract
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors... (More)
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors (PAC1, VPAC1, and VPAC2) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system. It is postulated that PACAP is involved in nociception. In support, abolishment of PACAP synthesis or reception leads to diminished pain responses, whereas systemic PACAP-38 infusion triggers pain behavior in animals and delayed migraine-like attacks in migraine patients without marked vasodilatory effects. In addition, increased plasma levels have been documented in acute migraine attacks and in cluster headache, in accordance with findings in experimental models of trigeminal activation. This suggest that the activation of the trigeminal system may result in elevated venous levels of PACAP, a change that can be reduced when headache is treated. The data presented in this review indicate that PACAP and its receptors may be promising targets for migraine therapeutics.
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- author
- Edvinsson, Lars LU ; Tajti, János ; Szalárdy, Levente and Vécsei, László
- organization
- publishing date
- 2018-03-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CGRP, Cluster headache, Migraine, PACAP, Receptors
- in
- Journal of Headache and Pain
- volume
- 19
- issue
- 1
- article number
- 21
- pages
- 7 pages
- publisher
- Springer
- external identifiers
-
- scopus:85043393473
- pmid:29523978
- ISSN
- 1129-2369
- DOI
- 10.1186/s10194-018-0852-4
- language
- English
- LU publication?
- yes
- id
- cb3792b2-b7ba-4daa-85e6-e074af55f3f8
- date added to LUP
- 2018-03-27 14:39:49
- date last changed
- 2024-06-25 14:39:56
@article{cb3792b2-b7ba-4daa-85e6-e074af55f3f8,
abstract = {{<p>Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors (PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub>) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system. It is postulated that PACAP is involved in nociception. In support, abolishment of PACAP synthesis or reception leads to diminished pain responses, whereas systemic PACAP-38 infusion triggers pain behavior in animals and delayed migraine-like attacks in migraine patients without marked vasodilatory effects. In addition, increased plasma levels have been documented in acute migraine attacks and in cluster headache, in accordance with findings in experimental models of trigeminal activation. This suggest that the activation of the trigeminal system may result in elevated venous levels of PACAP, a change that can be reduced when headache is treated. The data presented in this review indicate that PACAP and its receptors may be promising targets for migraine therapeutics.</p>}},
author = {{Edvinsson, Lars and Tajti, János and Szalárdy, Levente and Vécsei, László}},
issn = {{1129-2369}},
keywords = {{CGRP; Cluster headache; Migraine; PACAP; Receptors}},
language = {{eng}},
month = {{03}},
number = {{1}},
publisher = {{Springer}},
series = {{Journal of Headache and Pain}},
title = {{PACAP and its role in primary headaches}},
url = {{http://dx.doi.org/10.1186/s10194-018-0852-4}},
doi = {{10.1186/s10194-018-0852-4}},
volume = {{19}},
year = {{2018}},
}