The dorsal horn of the spinal cord is a complex laminar structure integrating exteroceptive signals from the primary afferent fibers into the central nervous system. The laminae of the spinal cord exhibit specialised roles and distinct processes occur across the axes of the dorsal horn. One of the most common in vivo approaches to recording spinal activity is single unit electrophysiology of cells that are believed to be representative of the subjects perception of stimuli. This approach has produced invaluable data but has not progressed in over half a century and fails to account for the specialised processes that occur in each lamina as well as the considerable cellular heterogeneity within and between laminae. In this thesis the use of linear multi-electrode array technology with 16 electrodes spaced 50 μm apart to have a total range of 750 μm that allows for simultaneous recordings across the laminae is developed and validated for the spinal dorsal horns of adult Sprague-Dawley rats. To do this a series of experiments were performed. The placement of the electrode was first optimised by creating a somatotopic map of evoked activity following hindpaw stimulation. A comprehensive series of electrical stimuli designed to induce differential primary afferent fiber activity were then given to establish how well the array could interpret fiber evoked activity. Mechanical and thermal stimulus paradigms were examined to evaluate the spatial distribution of responses across the dorsal horn; after optimisation the responses were then examined in the contexts of acute and chronic pain models. We found that the results of the unsorted multi-spike activity across the array correlated extremely well with predicted responses from single-unit studies in the existing literature. Fiber specific activation restricted along the dorso-ventral axis was detected as was the encoding of mechanical and thermal stimuli that were both innocuous and nocuous in nature. Comparisons between local field potentials and spike activity showed that multi-spike activity represented spinal processing of incoming signals significantly better. Induction of pain models strengthened the argument for the use of the technique by showing that it is capable of being used in both longitudinal and multi-treatment group studies. The approach produced vastly more data than the single-unit technique it builds upon with few drawbacks.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:765420 |
| Date | January 2018 |
| Creators | Greenspon, Charles |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/52849/ |
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