Hormone Induced "Migraine" and Attempts at Blocking Opiate Reward through NK1

Persistent Link:
http://hdl.handle.net/10150/321547
Title:
Hormone Induced "Migraine" and Attempts at Blocking Opiate Reward through NK1
Author:
Skinner, David P.
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release 12-May-2016
Abstract:
Migraine headache is one of the most common neurological disorders. While the mechanisms contributing to migraine pathophysiology have yet to be fully elucidated, the disproportionate number of post-pubescent, pre-menopausal women affected suggests a central role for female hormones, such as estrogen. The mechanism(s), however, by which estrogen contributes to migraine have yet to be deciphered. Cortical spreading depression (CSD) is associated with "Classic Migraine", now referred to as migraine with aura. Here we use a well-established animal model for migraine with aura to test the putative role of estrogen in the development of CSDs in awake and freely moving female rats. Beta estradiol administration in ovariectomized female rats resulted in a significant increase in CSD episodes over a 12-hour recording period. Additionally, beta estradiol administration in these rats promoted migraine-associated behavior, significantly reducing exploratory behavior (i.e., number of vertical rearing episodes) when compared to vehicle-treated controls. Critically, the increase in CSD episodes was completely abolished with pre-administration of ICI 182,780 a pure alpha and beta estrogen receptor antagonist. ICI 182,780administration also blocked beta estradiol-induced migraine-associated behaviors, restoring vertical rearing episodes to baseline levels. These data illustrate that an increase in estrogen levels in an animal that no longer produces estrogen (postmenopausal characteristic) can promote the development of CSDs. These data suggest that an estrogen receptor-mediated mechanism may drive episodes of migraine with aura and highlight the need for further investigation into estrogen's role in migraine.
Type:
text; Electronic Dissertation
Keywords:
Headache; Migraine; Neurokinin; Medical Pharmacology; Estradiol
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Medical Pharmacology
Degree Grantor:
University of Arizona
Advisor:
Vanderah, Todd W.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleHormone Induced "Migraine" and Attempts at Blocking Opiate Reward through NK1en_US
dc.creatorSkinner, David P.en_US
dc.contributor.authorSkinner, David P.en_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.releaseRelease 12-May-2016en_US
dc.description.abstractMigraine headache is one of the most common neurological disorders. While the mechanisms contributing to migraine pathophysiology have yet to be fully elucidated, the disproportionate number of post-pubescent, pre-menopausal women affected suggests a central role for female hormones, such as estrogen. The mechanism(s), however, by which estrogen contributes to migraine have yet to be deciphered. Cortical spreading depression (CSD) is associated with "Classic Migraine", now referred to as migraine with aura. Here we use a well-established animal model for migraine with aura to test the putative role of estrogen in the development of CSDs in awake and freely moving female rats. Beta estradiol administration in ovariectomized female rats resulted in a significant increase in CSD episodes over a 12-hour recording period. Additionally, beta estradiol administration in these rats promoted migraine-associated behavior, significantly reducing exploratory behavior (i.e., number of vertical rearing episodes) when compared to vehicle-treated controls. Critically, the increase in CSD episodes was completely abolished with pre-administration of ICI 182,780 a pure alpha and beta estrogen receptor antagonist. ICI 182,780administration also blocked beta estradiol-induced migraine-associated behaviors, restoring vertical rearing episodes to baseline levels. These data illustrate that an increase in estrogen levels in an animal that no longer produces estrogen (postmenopausal characteristic) can promote the development of CSDs. These data suggest that an estrogen receptor-mediated mechanism may drive episodes of migraine with aura and highlight the need for further investigation into estrogen's role in migraine.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectHeadacheen_US
dc.subjectMigraineen_US
dc.subjectNeurokininen_US
dc.subjectMedical Pharmacologyen_US
dc.subjectEstradiolen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Pharmacologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorVanderah, Todd W.en_US
dc.contributor.committeememberVanderah, Todd W.en_US
dc.contributor.committeememberFrench, Edward D.en_US
dc.contributor.committeememberBloom, Johnen_US
dc.contributor.committeememberHruby, Victor J.en_US
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