Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Oxytocin as a regulatory neuropeptide in the trigeminovascular system : Localization, expression and function of oxytocin and oxytocin receptors

Warfvinge, Karin LU orcid ; Krause, Diana N. LU ; Maddahi, Aida LU ; Grell, Anne Sofie LU ; Edvinsson, Jacob C.A. LU ; Haanes, Kristian A. and Edvinsson, Lars LU (2020) In Cephalalgia 40(12). p.1283-1295
Abstract

Background: Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents. Methods: The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments. Results: Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in... (More)

Background: Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents. Methods: The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments. Results: Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in numerous small to medium-sized neurons and thick axons characteristic of A∂ sensory fibers. Double immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and calcitonin gene-related peptide. In contrast, double immunostaining showed expression of the calcitonin gene-related peptide receptor component receptor activity-modifying protein 1 and oxytocin receptors in 23% of the small cells and in 47% of the medium-sized cells. Oxytocin immunofluorescence was observed only in trigeminal ganglia satellite glial cells. Oxytocin mRNA was below detection limit in the trigeminal ganglia. The trigeminal nucleus caudalis expressed mRNA for both oxytocin and its receptor. K+-evoked calcitonin gene-related peptide release from either isolated trigeminal ganglia or dura mater and it was not significantly affected by oxytocin (10 µM). Oxytocin directly constricted cranial arteries ex vivo (pEC50 ∼ 7); however, these effects were inhibited by the vasopressin V1A antagonist SR49059. Conclusion: Oxytocin receptors are extensively expressed throughout the rat trigeminovascular system and in particular in trigeminal ganglia A∂ neurons and fibers, but no functional oxytocin receptors were demonstrated in the dura and cranial arteries. Thus, circulating oxytocin may act on oxytocin receptors in the trigeminal ganglia to affect nociception transmission. These effects may help explain hormonal influences in migraine and offer a novel way for treatment.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A∂ fibers, CGRP, cranial arteries, migraine, oxytocin, Trigeminal ganglion
in
Cephalalgia
volume
40
issue
12
pages
1283 - 1295
publisher
Wiley-Blackwell
external identifiers
  • pmid:32486908
  • scopus:85085985726
ISSN
0333-1024
DOI
10.1177/0333102420929027
language
English
LU publication?
no
id
c635f4fa-5cf6-4d20-adda-f9a37ad89ada
date added to LUP
2020-07-02 13:41:33
date last changed
2024-04-17 11:28:26
@article{c635f4fa-5cf6-4d20-adda-f9a37ad89ada,
  abstract     = {{<p>Background: Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents. Methods: The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments. Results: Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in numerous small to medium-sized neurons and thick axons characteristic of A∂ sensory fibers. Double immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and calcitonin gene-related peptide. In contrast, double immunostaining showed expression of the calcitonin gene-related peptide receptor component receptor activity-modifying protein 1 and oxytocin receptors in 23% of the small cells and in 47% of the medium-sized cells. Oxytocin immunofluorescence was observed only in trigeminal ganglia satellite glial cells. Oxytocin mRNA was below detection limit in the trigeminal ganglia. The trigeminal nucleus caudalis expressed mRNA for both oxytocin and its receptor. K<sup>+</sup>-evoked calcitonin gene-related peptide release from either isolated trigeminal ganglia or dura mater and it was not significantly affected by oxytocin (10 µM). Oxytocin directly constricted cranial arteries ex vivo (pEC<sub>50</sub> ∼ 7); however, these effects were inhibited by the vasopressin V<sub>1A</sub> antagonist SR49059. Conclusion: Oxytocin receptors are extensively expressed throughout the rat trigeminovascular system and in particular in trigeminal ganglia A∂ neurons and fibers, but no functional oxytocin receptors were demonstrated in the dura and cranial arteries. Thus, circulating oxytocin may act on oxytocin receptors in the trigeminal ganglia to affect nociception transmission. These effects may help explain hormonal influences in migraine and offer a novel way for treatment.</p>}},
  author       = {{Warfvinge, Karin and Krause, Diana N. and Maddahi, Aida and Grell, Anne Sofie and Edvinsson, Jacob C.A. and Haanes, Kristian A. and Edvinsson, Lars}},
  issn         = {{0333-1024}},
  keywords     = {{A∂ fibers; CGRP; cranial arteries; migraine; oxytocin; Trigeminal ganglion}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1283--1295}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cephalalgia}},
  title        = {{Oxytocin as a regulatory neuropeptide in the trigeminovascular system : Localization, expression and function of oxytocin and oxytocin receptors}},
  url          = {{http://dx.doi.org/10.1177/0333102420929027}},
  doi          = {{10.1177/0333102420929027}},
  volume       = {{40}},
  year         = {{2020}},
}