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.
(Unpublished)
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.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| 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 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[img]](http://d-scholarship.pitt.edu/style/images/fileicons/application_pdf.png)
![[feed]](/images/feed-icon-32x32.png){kind=icon}