Download the full-sized PDF
Permanent link (DOI): https://doi.org/10.7939/R32116
This file is in the following communities:
|Faculty of Graduate Studies and Research|
This file is in the following collections:
|Theses and Dissertations|
Electrophysiological Signature of Neuropathic Pain Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Smith, Peter A (Department of Pharmacology and Center for Neuroscience)
- Examining committee member and department
Greer, John (Department of Physiology)
Callister, Robert (Department of Anatomy, University of Newcastle)
Tse, Fred (Department of Pharmacology)
Funk, Greg (Department of Physiology)
Kerr, Brad (Department of Anesthesiology and Pain Medicine)
Department of Pharmacology
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
Neuropathic pain afflicts 1.5-3% of the general population. It can be initiated by traumatic nerve injuries or diseases such as diabetic or post-herpetic neuropathy. Neuropathic pain is often initiated by abnormal spontaneous activity in sensory neurons and this provokes increased excitability of neurons in the dorsal horn of the spinal cord in a process known as “central sensitization”. However, different types of peripheral nerve injury may send different signals to the spinal cord. Therefore, electrophysiological and pharmacological methods were used to examine the properties of interneurons in substantia gelatinosa of rat spinal dorsal horn in two common neuropathic pain models: sciatic nerve axotomy and chronic constriction injury (CCI).
Axotomy increased synaptic excitation of putative excitatory neurons and decreased synaptic excitation of putative inhibitory neurons. Axotomy produced similar but weaker changes than CCI in electrophysiological properties of substantia gelatinosa neurons.
Axotomy reduced the functional expression of voltage gated Ca2+ channels and reduced expression presynaptic Ca2+ permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors on primary afferent terminals but CCI did not. Whereas CCI decreased the proportion of Ca2+ permeable AMPA receptors on the cell bodies of tonic firing putative inhibitory neurons, axotomy did not. Whereas CCI increased the proportion of Ca2+ permeable AMPA receptors in delay firing putative excitatory neurons, axotomy did not.
The changes in excitatory synaptic transmission produced by both axotomy and CCI likely contribute to the central sensitization that underlies the generation of neuropathic pain. The tendency for CCI to generate more profound changes in the dorsal horn than axotomy may relate to the stronger inflammatory response it produces and the probability that axotomy interrupts peripheral trophic support of presynaptic Ca2+ permeable AMPA receptors.
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
- Citation for previous publication
Chen, Yishen (2009). J. Physiology
- Date Uploaded
- Date Modified
- Audit Status
- Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 4013717
Last modified: 2015:10:12 16:06:00-06:00
Original checksum: 91ca29ad9b2fe8a26b9580254af97262
Well formed: true
Status message: Too many fonts to report; some fonts omitted. Total fonts = 1121
File title: Microsoft Word - 8 Chapter 6 correct version.docx
File author: Peter Smith
Page count: 320