Add abstract
Want to add your dissertation abstract to this database? It only takes a minute!
Search abstract
Search for abstracts by subject, author or institution
Want to add your dissertation abstract to this database? It only takes a minute!
Search for abstracts by subject, author or institution
by PATRICK GRENIER
Institution: | Queen's University |
---|---|
Year: | 2016 |
Keywords: | Ultra-low dose; tolerance; Neuropathic pain; Reward; Opioid; Gliosis; Adrenergic antagonists |
Posted: | 02/05/2017 |
Record ID: | 2105095 |
Full text PDF: | http://qspace.library.queensu.ca/bitstream/1974/14318/1/Grenier_Patrick_201604_PHD.pdf |
Aims: To determine the effects of ULD α2-AR antagonists on: i) sensory responses in morphine tolerant and nerve injured rats, ii) chronic morphine and nerve-injury induced spinal gliosis and neuronal activation, iii) morphine conditioned place preference (CPP), a paradigm that assesses the affective or emotional component of pain processing. Methods & Results: In a model of opioid tolerance, ULD atipamezole attenuated the loss of morphine antinociception in pain naïve rats, consistent with the literature. Next, a model of neuropathic pain (chronic constriction injury (CCI)) was employed and changes in responses to mechanical and thermal nociceptive stimuli were tracked over time. This was the first study to show positive effects of ULD α2-AR antagonists in alleviating pain hypersensitivity associated with nerve injury and attenuation of morphine tolerance in neuropathic animals. Using immunohistochemistry, tissue collected from all the animals was labeled to determine if molecular changes correlated with the behavior induced by ULD atipamezole. Morphine and CCI-induced gliosis in the spinal dorsal horn were attenuated in animals chronically administered ULD atipamezole. Neuronal activity inferred by c-Fos cell counts was likewise attenuated in neuropathic animals. Finally, through the use of the CPP paradigm, it was shown ULD atipamezole is neither rewarding nor aversive on its own, but disrupts the development of morphine CPP in CCI animals, but not the sham or pain naïve animals. Currently, experimental evidence suggests a reduction in opioid reward in the neuropathic rats. Conclusion: ULD α2-AR antagonist atipamezole inhibits morphine tolerance and enhances opioid analgesia in pain naïve and chronic pain states, alleviates the mechanical hypersensitivity following nerve injury, inhibits chronic morphine and nerve injury-induced glial and neuronal activation in the spinal dorsal horn, and disrupts opioid reward in chronic pain states. Advisors/Committee Members: Catherine M Cahill, Mary C Olmstead (supervisor).
Want to add your dissertation abstract to this database? It only takes a minute!
Search for abstracts by subject, author or institution
Physiological and Antioxidant Properties of Centel...
|
|
A Neuron-Specific Protein found in Skeletal Muscle
New Frontiers for GAP-43
|
|
Bismuth-Ethanedithiol
A Potential Drug to Treat Biofilm Infections of Me...
|
|
The Effect of Ozone on the Growth and Development ...
|
|
Biocontrol of Cereal Pathogens
|
|
An Investigation of the Mechanism of PAX7 Mediated...
|
|
Ecological Study of the Role of Highly Processed M...
|
|
Farmers' Rural Community Attachment
A Structural Symbolic Interactionist Explanation
|
|