Assessing Pain and Treatment Responsiveness in a Patient Cohort and Mouse Model of Inflammatory Arthritis Using Neurobiophotonics
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(Thesis)
Date
2021
Authors
Lees, Florence
Editors
Advisors
Crotti, Tania
Hutchinson, Mark
Hutchinson, Mark
Journal Title
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Thesis
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Abstract
Rheumatoid Arthritis (RA) is characterised by inflammation, damage to the joint and persistent pain. The current methods used to assess pain in RA patients are limited as they are highly subjective and reliant on the patient self-reporting; this can often misalign with what is observed clinically. This disconnect can have significant consequences for the individual, with failed management of their pain, and to the economy with the inappropriate prolonged use of very expensive therapies, for example immunotherapies. Traditionally, pain in RA has been focused on the peripheral joint. However, it is now appreciated that there is a bidirectional relationship between the peripheral, spinal and brain immune systems. Glial cells such as microglia and astrocytes have been shown to play a role in the persistence of pain in RA and similar disease states,
The studies within this thesis investigate the neuroimmune elements of RA and explore the application of novel imaging techniques to objectively assess pain. A collagen antibody induced arthritis (CAIA) mouse model was used to investigate the effect of parthenolide on inflammation, hypernociception and spinal glial reactivity. This was examined via immunohistochemistry of paw, spinal cord, and brain tissue. Micro-computer tomography was used to assess bone loss along with behaviour testing for pain like behaviour. The CAIA model was also used to determine if a higher dose of CAIA antibodies would enable a more optimised CAIA model via assessment of inflammation within the central and peripheral nervous system. the use of hyperspectral imaging was utilised in the CAIA model along with immunohistochemistry to examine if there was a spectral change within the central nervous system. It was demonstrated that parthenolide was able to reduce inflammation within paw tissue and glial reactivity within the brain and spinal cord region. A higher dose of CAIA antibodies was able to elicit inflammation within the central and peripheral nervous system. Finally, patient samples from individuals with RA were used to determine if spectral differences were measurable between inactive and active disease state RA patient samples via hyperspectral imaging. Hyperspectral imaging of the synovial tissue was able to be used in human patients to objectively separate between disease state and pain state.
School/Discipline
School of Medicine
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2022
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