Neuromyelitis optica is a severe autoimmune neuroinflammatory disorder characterised by longitudinally extensive myelitis and severe optic neuritis. An oft-neglected symptom of the condition is severe, intractable chronic pain that can be detrimental to quality of life and is marked out by its severity and prevalence in comparison to the related disorder, multiple sclerosis. The experiments within this thesis make use of both conventional and advanced MRI techniques applied to the spinal cord and brain, and <sup>1</sup>H NMR spectroscopy of blood plasma to explore the mechanisms driving chronic pain in NMO. The principle findings are: i. Thoracic lesions are associated with greater pain, irrespective of lesion length or cervical lesion volume. They are associated with spinothalamic tract damage in the cervical cord that correlates with the severity of pain. A possible autonomic aetiology is proposed. ii. Periaqueductal grey (PAG) to dorsolateral prefrontal cortex and to pregenual anterior cingulate cortex functional connectivity is correlated with pain severity, conversely PAG to rostroventromedial medulla connectivity is negatively associated with pain severity. Disruption of descending pain modulatory circuits is considered. iii. PAG glutamate concentration is negatively correlated with pain scores and is higher in low pain patients compared to controls and high pain patients. The discussion includes consideration of pain vulnerability. Chronic pain in NMO can devastate lives. The studies undertaken in this thesis are some of the earliest MRI imaging studies directed at understanding pain in NMO and the association of pain with thoracic lesions and the aberrations in the descending pain modulatory network are novel findings. There is more to be done and my hope is that this body of work will serve as a stepping-stone to a better understanding of chronic pain in NMO and the future development of effective treatments.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:740948 |
| Date | January 2017 |
| Creators | Tackley, George |
| Contributors | Palace, Jacqueline ; Tracey, Irene ; Kong, Yazhuo |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:db003fe8-4bca-40c1-99d2-cff07bf3eaa0 |
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