Current Portfolio
- Epilepsy
- Bone disease
- Nanotoxicity testing
- Abdominal pain studies
- Brain cell imaging
- Huntington's disease
- Breast Cancer
- Viral encephalitis
- Chronic pain in arthritis and fibromyalgia
- Bacterial infection in cystic fibrosis
- Advances in human neuroscience
- Neurofibromatosis
- Hypersecretion of mucus in asthma
- Premature birth
- A clearer picture of pain relief
- Tissue engineering of human liver
- Creating knockout tissues
- Skin cancer
- Magnetoencephalography (MEG)
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Abdominal pain studies
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2010 – 2013 PhD Studentship A novel pre-clinical human model of visceral painMr Charles H. Knowles, MBBChir, PhD, FRCS |
Although the processes underlying visceral nociception (internal processing and encoding of pain) have been extensively studied in small animal models, differences exist in drug efficacy between rodents and man. There is currently no human model to study electrophysiological responses to chemical or mechanical stimuli, nor to modulate this process with novel drugs.
Unexplained abdominal pain presents a significant healthcare burden and one in which there is a current lack of effective treatments, partly because of insufficient methods to directly study in nerves how this pain occurs.
Drug companies, despite recent considerable investment and promising research studies, have failed to develop drugs with better than modest efficacy in clinical trials. One step in developing new drugs for pain is the need to show that the drug is effective in reducing responses to painful stimuli, and in particular in reducing the firing of pain transmitting nerves.
The aim of this project is to continue the development of a model on which human visceral afferent neuronal responses can be reproducibly measured and modulated in vitro. Ethically obtained, surgically-derived full thickness colonic tissues and associated tissues, will be used to obtain recordings from the small mesenteric nerves in an ex vivo system. A series of studies will determine:
i) Basic responses to mechanical stimuli using established stimulation paradigms.
ii) The role of immune-inflammatory mediators by comparison of basal and mechanically-stimulated afferent activities in normal and inflamed tissues and by the effect of mucosal supernatants obtained from human acute and chronic inflammatory disease on afferent activities in normal tissue
iii) A further study will attempt to correlate in vivo pharmacological reductions of colonic mucosal multimodal pain responses with attenuation of afferent activity in vitro.
iv) Finally, specific receptor ligand-antagonist studies will be performed to establish early proof of principal for drug testing
Some expected outcomes include the replacement of animals used in studies directed to visceral pain and progression towards a platform for testing drug efficacy in humans before costly phase II clinical trials.