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IDENTIFICATION OF FACTORS CONTRIBUTING TO THE INITIATION OF MIGRAINE: THE IMPACT OF SEX-, STRESS-, AND SYMPATHETIC-DEPENDENT CHANGES IN THE DURA

McIlvried, Lisa (2015) IDENTIFICATION OF FACTORS CONTRIBUTING TO THE INITIATION OF MIGRAINE: THE IMPACT OF SEX-, STRESS-, AND SYMPATHETIC-DEPENDENT CHANGES IN THE DURA. Doctoral Dissertation, University of Pittsburgh.

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Abstract

Given evidence that the pain of migraine originates in the peripheral dural afferents, and that sterile inflammation contributes to the activation and sensitization of dural afferents, the question addressed in this dissertation was, how is inflammation in the dura initiated, which could then lead to the start of a migraine attack? Immune cells are one well-known primary source of inflammatory mediators and likely, at least in part, responsible for sterile dural inflammation. Therefore, changes in dural immune cells were characterized in association with three, key clinical features of migraine—that migraine is more common in women than in men, stress is the most common trigger for a migraine attack, and sympathetic dysregulation is observed in migraineurs. Dural immune cells were obtained for flow cytometry and fluorescence activated cell sorting from male or female, naïve or stressed, intact or with surgical denervation of sympathetic post-ganglionic neurons, adult Sprague Dawley rats. The total proportion of immune cells in the dura was identified for the first time, as well as the presence of lymphoid derived dural immune cells, even in naïve animals. Immune cell subtypes (macrophages in males, and T-cells in females) increased with a delay after stress, suggesting for the first time a possible role for T-cells in migraine. Furthermore, pro- (TNFα and IL-6) and anti- (IL-10 and POMC) inflammatory mediator mRNA expression was up- and down-regulated, respectively, in myeloid and lymphoid dural immune cells with a delay after stress, particularly in females, suggesting that a shift in the balance of pro- and anti-inflammatory mediators may also contribute to the initiation of a migraine attack. This dissertation expands the current view of the dura, revealing it to be a much more immune rich and complex tissue than previously appreciated. Most importantly, this work underscores the possibility that it may not only be possible, but necessary to differentially treat migraine in men and women.


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Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
McIlvried, Lisalam98@pitt.eduLAM98
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGebhart, Gerald Fgebhartgf@upmc.edu
Thesis AdvisorGold, Michael Smsg22@pitt.eduMSG22
Committee MemberBorghesi, Lisa Aborghesi@pitt.eduBORGHESI
Committee MemberDavis, Brian Mbmd1@pitt.eduBMD1
Committee MemberHorn, John Pjph@pitt.eduJPH
Committee MemberSved, Alan Fsved@pitt.eduSVED
Committee MemberDussor, GregoryGregory.Dussor1@utdallas.edu
Date: 20 August 2015
Date Type: Publication
Defense Date: 18 June 2015
Approval Date: 20 August 2015
Submission Date: 20 August 2015
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 162
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: headache, autonomic, pain, meninges
Date Deposited: 20 Aug 2015 18:02
Last Modified: 15 Nov 2016 14:30
URI: http://d-scholarship.pitt.edu/id/eprint/26031

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