Memorial University DAI: A study of the role of spinal prostaglandins and nitric oxide early after nerve injury

advanced search

Digital Archives Initiative
Memorial University - Electronic Theses and Dissertations 4

menu off

add document to favorites : add page to favorites : reference url

back to results : previous : next

Search this object:

0 hit(s) :: previous hit : next hit

View:

previous page : next page

Document Description

Title	A study of the role of spinal prostaglandins and nitric oxide early after nerve injury
Author	O'Rielly, Darren Douglas, 1977-
Description	Thesis (Ph.D)--Memorial University of Newfoundland, 2009. Medicine
Date	2008
Pagination	xxxiv, 264 leaves : ill. (some col.)
Subject	Allodynia; Nervous system--Wounds and injuries; Nitric oxide--Physiological effect; Prostaglandins--Physiological effect; Lumbosacral Plexus--injuries; Lumbosacral Plexus--physiopathology; Nitric Oxide; Prostaglandins E
Subject.MESH	Lumbosacral Plexus--injuries; Lumbosacral Plexus--physiopathology; Nitric Oxide; Prostaglandins E
Degree	Ph.D
Degree Grantor	Memorial University of Newfoundland. Faculty of Medicine
Discipline	Medicine
Language	Eng
Notes	Includes bibliographical references (leaves 213-264).
Abstract	Allodynia is an abnormal state in which pain is triggered by innocuous sensory stimuli. Previous work in our laboratory has shown that L5/L6 spinal nerve ligation (SNL) induces robust mechanical allodynia in the rat which consists of two distinct phases: (a) an early spinal prostaglandin (PG)-dependent phase lasting approximately seven to ten days; and (b) a delayed PG-independent phase lasting at least seventy days. Importantly, the former is a prerequisite to and a trigger for the more complex and time-dependent changes underlying long-term, irreversible allodynia. Interfering with critical signaling events early after nerve injury is a logical strategy by which chronic neuropathic pain might be prevented. Such an approach requires a clear understanding of the sequence, time-course and pharmacology of these early signals. -- In light of the apparent pathogenic role of spinal PG early after nerve injury, the present research investigated the SNL-induced changes in spinal PG synthesis and signaling, their relevance to the development of spinal hyperexcitability and allodynia, and the mechanisms underlying the changes in PG synthesis and signaling in the spinal PG-dependent phase. The specific objectives were: -- (1) To characterize the effect of SNL on A- and C-fiber mediated reflex responses (AFRR and CFRR, respectively) in the affected hind limb, and to determine the temporal and spatial relationship of these changes to SNL-induced allodynia. -- (2) To determine if the SNL-induced changes in the AFRR and CFRR (i.e. spinal hyperexcitability) are spinal PG-dependent, and if so, to determine the relevant cyclooxygenase (COX) isoform(s). -- (3) To determine if SNL triggers the activation of nuclear factor kappa-B (NFκB) in the affected spinal cord which initiate the delayed induction of spinal COX-2. -- (4) To determine if the sensitivity to PG E type (PGE 2 ) is exaggerated during spinal PG-dependent allodynia, and if this abnormal state is limited to the affected spinal cord three days after SNL. -- (5) To determine if PG-dependent spinal hyperexcitability and mechanical allodynia are mediated by E-type prostaglandin (EP) receptors, and to investigate the changes in the expression of spinal EP 1-3 receptor subtypes and the glycine-α3 receptor subunit (GLY-α3R) three days after SNL. -- (6) To determine if disrupting spinal PG synthesis/signaling immediately after SNL (i.e. pre-emptive treatment) prevents the development of PG-dependent spinal hyperexcitability and mechanical allodynia. -- (7) To determine if spinal PG-dependent hyperexcitability is affected by the SNL-induced generation of spinal nitric oxide (NO), and if so, to investigate relevant NO synthase (NOS) isoform(s).
Type	Text
Resource Type	Electronic thesis or dissertation
Format	Image/jpeg; Application/pdf
Source	Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifier	a3241893
Rights	The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
Collection	Electronic Theses and Dissertations
Scanning Status	Completed
PDF File	(32.74 MB) -- http://collections.mun.ca/PDFs/theses/ORielly_DarrenDouglas.pdf
CONTENTdm file name	60691.cpd