- Title
- Investigation of visceral sensory processing mechanisms in the superficial dorsal horn of the spinal cord
- Creator
- Farrell, Kristen Elise
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2017
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Pain is the most common symptom of inflammatory diseases of viscera or the gastrointestinal tract. Importantly, pain occurs during active disease and often persists during clinical remission. The specific functional mechanisms underlying the development and maintenance of visceral pain are not known. To date, functional studies have focussed on the peripheral nervous system, using gut-nerve preparations, in animal models of visceral hypersensitivity. Clinical studies, however, suggest changes in the central nervous system CNS contribute to altered sensory perception in visceral inflammation. This thesis first explored the central mechanisms underlying visceral hypersensitivity in animal models of visceral inflammation. I completed a systematic review and found extensive evidence for CNS plasticity, particularly within the spinal cord dorsal horn (DH), in animal models of visceral inflammation. I also found no studies had examined the functional properties of DH neurons during visceral inflammation even though these properties are critical determinants of neuron output and altered signaling to the brain. Next, to study the functional properties of neurons that received colonic inputs, I developed an in vivo preparation that permitted wholecell electrophysiological recording from DH neurons in intact adult mice. I showed that in naïve animals, neurons with colonic inputs responded to visceral stimulation with predominately subthreshold synaptic activity. Their membrane and synaptic properties also differed from neurons lacking colonic inputs. I next repeated these experiments in a mouse model of mild colitis. During colitis the responses of DH neurons to visceral and cutaneous stimulation and their synaptic properties were altered in a manner that would make DH neurons more excitable. Conversely, several measures of intrinsic excitability were decreased following colitis. These data suggest visceral inflammation has complex effects on the functional properties of DH neurons and likely reflects the crucial role the spinal cord plays in modulating sensory inputs from the viscera.
- Subject
- spinal cord; dorsal horn; thesis by publication; colitis; pancreatitis; central sensitization; patch-clamp; viscera; synaptic current; pain; colorectal distension
- Identifier
- http://hdl.handle.net/1959.13/1335508
- Identifier
- uon:27443
- Rights
- Copyright 2017 Kristen Elise Farrell
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 10 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 129 KB | Adobe Acrobat PDF | View Details Download |