Infra-slow oscillations in chronic orofacial neuropathic pain and the effects of palmitoylethanolamide
Access status:
Open Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Alshelh, ZeynabAbstract
For centuries, chronic pain was denied as being real by physicians, mainly because there was no evidence of tissue damage. The lack of understanding of the neural mechanisms underlying chronic pain, particular that arising from nervous system damage, has hindered treatment development ...
See moreFor centuries, chronic pain was denied as being real by physicians, mainly because there was no evidence of tissue damage. The lack of understanding of the neural mechanisms underlying chronic pain, particular that arising from nervous system damage, has hindered treatment development which has led to the over-prescription of opioids. Whilst the brain circuitry responsible for the perception of acute painful stimuli have been mapped in both animal studies and studies using brain imaging in awake humans, the circuitry responsible for the initiation and maintenance of chronic pain remain unknown. Over the past few decades, many human brain imaging investigations have shown that neuropathic pain is associated with altered brain rhythms and in particular thalamocortical dysrhythmia. In addition, animal studies have shown that neuropathic pain is associated with altered non-neural function including microglial and astrocyte activation at the level of the primary afferent synapse. These results have led to theories that non-neuronal cells may be crucial for the initiation and maintenance of chronic pain, particularly chronic neuropathic pain. It has been a long held view that astrocytes mainly play the role of neural support in the central nervous system, however, these cells are also capable of controlling neural function. In fact, astrocytes have access to every neural synapse and animal models of chronic neuropathic pain have shown that targeting astrocytes can control pain intensity. As such, the focus of this thesis is to identify the role of astrocytes in modulating neural function in chronic neuropathic pain and to determine whether reducing astrocyte activity can reduce pain intensity. There are three main investigations that make up this thesis, the first describes an experimental procedure whereby on-going patterns of neural activity were assessed in patients with orofacial neuropathic pain using resting state functional magnetic resonance imaging. The second attempts to measure an anatomical marker of astrocyte activation. And the final investigation describes an experimental procedure whereby patients with orofacial neuropathic pain were administered an astrocyte modulator, palmitoylethanolamide (PEA) and neural activity was compared before and after treatment.
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See moreFor centuries, chronic pain was denied as being real by physicians, mainly because there was no evidence of tissue damage. The lack of understanding of the neural mechanisms underlying chronic pain, particular that arising from nervous system damage, has hindered treatment development which has led to the over-prescription of opioids. Whilst the brain circuitry responsible for the perception of acute painful stimuli have been mapped in both animal studies and studies using brain imaging in awake humans, the circuitry responsible for the initiation and maintenance of chronic pain remain unknown. Over the past few decades, many human brain imaging investigations have shown that neuropathic pain is associated with altered brain rhythms and in particular thalamocortical dysrhythmia. In addition, animal studies have shown that neuropathic pain is associated with altered non-neural function including microglial and astrocyte activation at the level of the primary afferent synapse. These results have led to theories that non-neuronal cells may be crucial for the initiation and maintenance of chronic pain, particularly chronic neuropathic pain. It has been a long held view that astrocytes mainly play the role of neural support in the central nervous system, however, these cells are also capable of controlling neural function. In fact, astrocytes have access to every neural synapse and animal models of chronic neuropathic pain have shown that targeting astrocytes can control pain intensity. As such, the focus of this thesis is to identify the role of astrocytes in modulating neural function in chronic neuropathic pain and to determine whether reducing astrocyte activity can reduce pain intensity. There are three main investigations that make up this thesis, the first describes an experimental procedure whereby on-going patterns of neural activity were assessed in patients with orofacial neuropathic pain using resting state functional magnetic resonance imaging. The second attempts to measure an anatomical marker of astrocyte activation. And the final investigation describes an experimental procedure whereby patients with orofacial neuropathic pain were administered an astrocyte modulator, palmitoylethanolamide (PEA) and neural activity was compared before and after treatment.
See less
Date
2018-06-04Licence
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Faculty of Medicine and HealthDepartment, Discipline or Centre
Department of Anatomy and Histology, Laboratory of Neural ImagingAwarding institution
The University of SydneyShare