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Expression of messenger molecules and receptors in rat and human sphenopalatine ganglion indicating therapeutic targets

Steinberg, Anna; Frederiksen, Simona D.; Blixt, Frank W. LU ; Warfvinge, Karin LU and Edvinsson, Lars LU (2016) In Journal of Headache and Pain 17(1).
Abstract

Background: Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters... (More)

Background: Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT1B,1D,1F) were examined. Methods: SPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT1B,1D,1F receptors, and botulinum toxin receptor elements. Results: We found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT1B receptors were in addition found in the walls of intraganglionic blood vessels. Conclusions: Recent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation’s drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
5-HT receptor agonists, BoNT-A, Botox receptors, Parasympathetic signaling transmitters, Sphenopalatine ganglion
in
Journal of Headache and Pain
volume
17
issue
1
publisher
Springer
external identifiers
  • Scopus:84984891086
ISSN
1129-2369
DOI
10.1186/s10194-016-0664-3
language
English
LU publication?
yes
id
f69fb5f2-e86d-4eb4-adf6-efb83dd152f4
date added to LUP
2016-09-28 11:13:04
date last changed
2016-11-14 09:43:05
@misc{f69fb5f2-e86d-4eb4-adf6-efb83dd152f4,
  abstract     = {<p>Background: Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT<sub>1B,1D,1F</sub>) were examined. Methods: SPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT<sub>1B,1D,1F</sub> receptors, and botulinum toxin receptor elements. Results: We found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT<sub>1B</sub> receptors were in addition found in the walls of intraganglionic blood vessels. Conclusions: Recent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation’s drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.</p>},
  author       = {Steinberg, Anna and Frederiksen, Simona D. and Blixt, Frank W. and Warfvinge, Karin and Edvinsson, Lars},
  issn         = {1129-2369},
  keyword      = {5-HT receptor agonists,BoNT-A,Botox receptors,Parasympathetic signaling transmitters,Sphenopalatine ganglion},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {ARRAY(0x7585270)},
  series       = {Journal of Headache and Pain},
  title        = {Expression of messenger molecules and receptors in rat and human sphenopalatine ganglion indicating therapeutic targets},
  url          = {http://dx.doi.org/10.1186/s10194-016-0664-3},
  volume       = {17},
  year         = {2016},
}