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Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans

Frederiksen, Simona Denise; Warfvinge, Karin LU ; Ohlsson, Lena LU and Edvinsson, Lars LU (2018) In Neuroscience 393. p.319-332
Abstract

Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP... (More)

Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP type I receptor (PAC1) and vasoactive intestinal peptide/PACAP receptors 1/2 (VPAC1/2). 5-Hydroxytryptamine (5-HT) receptors were expressed in neuronal somas in rat and human TG (human TG frequency: 5-HT1D > 5-HT1B/1F). Synaptosomal-associated protein 25 kDa (SNAP25) was primarily expressed in SGCs in humans, and neurons in rats, while synaptic vesicle glycoprotein 2A (SV2-A) was confined to SGCs and some neurons in rats and humans. Occasionally, PACAP-38-positive cells also expressed VPAC1, SNAP25 and SV2-A. VPAC1 was generally detected in SGCs enveloping PACAP-38-positive and -negative neuronal somas. Our study revealed potential sites of actions for anti-headache drugs such as PACAP receptor antagonists, Lasmiditan (5-HT1F agonist) and Botox (blocks exocytosis through SV2-A/SNAP25) in rat and human TG and considerable overlap between species in expression to specific cell types, except for VPAC1 and SNAP25.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Botox, CGRP, PACAP, PACAP receptors, sensory nervous system, serotonin receptors
in
Neuroscience
volume
393
pages
14 pages
publisher
Elsevier
external identifiers
  • scopus:85055900702
ISSN
0306-4522
DOI
10.1016/j.neuroscience.2018.10.004
language
English
LU publication?
yes
id
7bd65b9c-9b2a-4cd6-a1a4-483eb4855fc8
date added to LUP
2018-11-14 12:49:16
date last changed
2019-08-14 04:27:07
@article{7bd65b9c-9b2a-4cd6-a1a4-483eb4855fc8,
  abstract     = {<p>Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP type I receptor (PAC<sub>1</sub>) and vasoactive intestinal peptide/PACAP receptors 1/2 (VPAC<sub>1/2</sub>). 5-Hydroxytryptamine (5-HT) receptors were expressed in neuronal somas in rat and human TG (human TG frequency: 5-HT<sub>1D</sub> &gt; 5-HT<sub>1B/1F</sub>). Synaptosomal-associated protein 25 kDa (SNAP25) was primarily expressed in SGCs in humans, and neurons in rats, while synaptic vesicle glycoprotein 2A (SV2-A) was confined to SGCs and some neurons in rats and humans. Occasionally, PACAP-38-positive cells also expressed VPAC<sub>1</sub>, SNAP25 and SV2-A. VPAC<sub>1</sub> was generally detected in SGCs enveloping PACAP-38-positive and -negative neuronal somas. Our study revealed potential sites of actions for anti-headache drugs such as PACAP receptor antagonists, Lasmiditan (5-HT<sub>1F</sub> agonist) and Botox (blocks exocytosis through SV2-A/SNAP25) in rat and human TG and considerable overlap between species in expression to specific cell types, except for VPAC<sub>1</sub> and SNAP25.</p>},
  author       = {Frederiksen, Simona Denise and Warfvinge, Karin and Ohlsson, Lena and Edvinsson, Lars},
  issn         = {0306-4522},
  keyword      = {Botox,CGRP,PACAP,PACAP receptors,sensory nervous system,serotonin receptors},
  language     = {eng},
  pages        = {319--332},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2018.10.004},
  volume       = {393},
  year         = {2018},
}