The neurological consequences of non freezing cold injury
<p>Non-freezing cold injury is a clinical syndrome characterised by altered sensory perception following prolonged exposure to cool temperatures. Acutely there is loss of sensation but after several hours or days, pain emerges in the distal extremities, which may last months or years after inj...
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| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1826315804695592960 |
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| author | Vale, T |
| author2 | Bennett, D |
| author_facet | Bennett, D Vale, T |
| author_sort | Vale, T |
| collection | OXFORD |
| description | <p>Non-freezing cold injury is a clinical syndrome characterised by altered sensory perception following prolonged exposure to cool temperatures. Acutely there is loss of sensation but after several hours or days, pain emerges in the distal extremities, which may last months or years after injury. The pain is characteristically more severe when the affected skin is cooled, at temperatures that would not have elicited pain before injury. The condition is well known in the military, most notoriously in The First World War as “Trench Foot”. New cases are still seen in the British Military in the 21st Century. There has never been a detailed study to address the neurological phenotype of patients with chronic symptoms. In this thesis 80 such patients underwent neurological phenotyping and assessment for the presence of neuropathic pain. The data in this thesis provide clear evidence for the presence of a sensory neuropathy with severe neuropathic pain due to small fibre neural injury, as demonstrated by abnormalities on quantitative sensory testing and reduced intraepidermal nerve fibre densities. Soldiers of African heritage have long been recognised to be predisposed to injury, raising the question of whether there could be a genetic contribution to this syndrome. Using a whole genome sequencing approach, a variant in the voltage gated sodium channel gene, SCN9A, was found to be over-represented in the cohort. Furthermore, in cellular electrophysiology experiments, the variant bestowed gain of function effects on HEK293 cells, but only at cool temperatures, providing a molecular correlate for the cold-aggravated pain seen in patients. Assessment of axonal excitability by threshold tracking suggests that there may be a reduction in slow potassium current, which has been shown to associate with neuropathic pain and cold allodynia. This thesis provides an evidence base for assessment and management of patients and suggests abnormalities in both sodium and potassium channel function, which warrant further research. This could have important implications for targeted therapy.</p> |
| first_indexed | 2024-03-06T19:23:48Z |
| format | Thesis |
| id | oxford-uuid:1b082ffd-0165-4b4a-9ab3-1224d62bf3ce |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:32:55Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:1b082ffd-0165-4b4a-9ab3-1224d62bf3ce2024-12-01T16:03:38ZThe neurological consequences of non freezing cold injuryThesishttp://purl.org/coar/resource_type/c_db06uuid:1b082ffd-0165-4b4a-9ab3-1224d62bf3ceNeuropathic painNon freezing cold injuryEnglishHyrax Deposit2021Vale, TBennett, D<p>Non-freezing cold injury is a clinical syndrome characterised by altered sensory perception following prolonged exposure to cool temperatures. Acutely there is loss of sensation but after several hours or days, pain emerges in the distal extremities, which may last months or years after injury. The pain is characteristically more severe when the affected skin is cooled, at temperatures that would not have elicited pain before injury. The condition is well known in the military, most notoriously in The First World War as “Trench Foot”. New cases are still seen in the British Military in the 21st Century. There has never been a detailed study to address the neurological phenotype of patients with chronic symptoms. In this thesis 80 such patients underwent neurological phenotyping and assessment for the presence of neuropathic pain. The data in this thesis provide clear evidence for the presence of a sensory neuropathy with severe neuropathic pain due to small fibre neural injury, as demonstrated by abnormalities on quantitative sensory testing and reduced intraepidermal nerve fibre densities. Soldiers of African heritage have long been recognised to be predisposed to injury, raising the question of whether there could be a genetic contribution to this syndrome. Using a whole genome sequencing approach, a variant in the voltage gated sodium channel gene, SCN9A, was found to be over-represented in the cohort. Furthermore, in cellular electrophysiology experiments, the variant bestowed gain of function effects on HEK293 cells, but only at cool temperatures, providing a molecular correlate for the cold-aggravated pain seen in patients. Assessment of axonal excitability by threshold tracking suggests that there may be a reduction in slow potassium current, which has been shown to associate with neuropathic pain and cold allodynia. This thesis provides an evidence base for assessment and management of patients and suggests abnormalities in both sodium and potassium channel function, which warrant further research. This could have important implications for targeted therapy.</p> |
| spellingShingle | Neuropathic pain Non freezing cold injury Vale, T The neurological consequences of non freezing cold injury |
| title | The neurological consequences of non freezing cold injury |
| title_full | The neurological consequences of non freezing cold injury |
| title_fullStr | The neurological consequences of non freezing cold injury |
| title_full_unstemmed | The neurological consequences of non freezing cold injury |
| title_short | The neurological consequences of non freezing cold injury |
| title_sort | neurological consequences of non freezing cold injury |
| topic | Neuropathic pain Non freezing cold injury |
| work_keys_str_mv | AT valet theneurologicalconsequencesofnonfreezingcoldinjury AT valet neurologicalconsequencesofnonfreezingcoldinjury |