ERA

Download the full-sized PDF of The effect of long-term interleukin-1 beta exposure on sensory neuron electrical membrane properties: implications for neuropathic painDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R3QT3S

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

The effect of long-term interleukin-1 beta exposure on sensory neuron electrical membrane properties: implications for neuropathic pain Open Access

Descriptions

Other title
Subject/Keyword
ion channels
electrophysiology
central sensitization
peripheral nerve injury
excitability
sensory neurons
dorsal root ganglion
cell culture
interleukin-1 beta
neuropathic pain
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Stemkowski, Patrick
Supervisor and department
Smith, Peter (Pharmacology)
Examining committee member and department
Dryden, Bill (Pharmacology)
Tse, Fred (Pharmacology)
Department
Centre for Neuroscience
Specialization

Date accepted
2011-01-10T22:55:27Z
Graduation date
2011-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The effect of interleukin-1 beta (IL-1β) on the electrical properties of sensory neurons was assessed at comparable levels and exposure times to those found in animal models of neuropathic pain. Experiments involved whole cell current- or voltage-clamp recordings from rat dorsal root ganglion (DRG) neurons in defined medium, neuron enriched cultures. 5-6 days exposure to 100 pM IL-1β produced neuron specific effects. These included an increase in the excitability of medium diameter and small diameter isolectin B4 (IB4)-positive neurons that was comparable to that found after peripheral nerve injury. By contrast, a reduction in excitability was observed in large diameter neurons, while no effect was found in small diameter IB4-negative neurons. Further characterization of changes in medium and small IB4-positive neurons revealed that some, but not all, effects of IL-1β were mediated through its receptor, IL-1RI. Using appropriate voltage protocols and/or ion substitutions, it was found that neuron specific changes in several ionic currents, including alterations in hyperpolarization activated inward current (IH) and decreases in various K+ currents contribute to the increased excitability produced by IL-1β. Overall, these studies revealed that: 1. The effects of long-term exposure of DRG neurons to IL-1β are reflective of the enduring increase in primary afferent excitability reported after peripheral nerve injury. This expands the recognized role of IL-1β in acute inflammatory pain to neuropathic pain. 2. Hyperexcitability in medium neurons exposed to IL-1β likely includes mixed populations of neurons corresponding to nociceptive and non-nociceptive primary afferent fibres and, therefore, has relevance to hyperalgesia and allodynia, respectively. 3. The responsiveness of small IB4-positive neurons, but not IB4-negative, to prolonged IL-1β exposure is consistent with the suggestion that small IB4-negative afferents are involved in inflammatory pain, while small IB4-positive afferents are involved neuropathic pain. 4. The identification of receptor mediated effects and several contributing ionic mechanisms, may have relevance to the development of new therapeutic approaches to neuropathic pain. 5. IL-1β can contribute to increased neuronal excitability by mechanisms that are independent of IL-1RI signalling. This should be taken into account when targeting IL-1β, or more specifically IL-1RI, in the management of neuropathic pain.
Language
English
DOI
doi:10.7939/R3QT3S
Rights
License granted by Patrick Stemkowski (pstemkowski@pmcol.ualberta.ca) on 2011-01-10T17:00:40Z (GMT): 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 the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein 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

File Details

Date Uploaded
Date Modified
2014-05-01T03:21:45.423+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 12449210
Last modified: 2015:10:12 15:37:35-06:00
Filename: Stemkowski_Patrick_Spring 2011.pdf
Original checksum: 3d239654d5c76c8dec3ad221985fdc19
Well formed: true
Valid: true
Status message: Too many fonts to report; some fonts omitted. Total fonts = 2542
File title: Pats Thesis revised intro and chapter 1.pdf
File author: Patrick Stemkowski
Page count: 508
Activity of users you follow
User Activity Date